Late Breaking Abstracts
July 2013 | Volume 62 | Suppl. 1A | www.diabetes.org/diabetes
Late Breaking Abstracts
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Subject Index
LB56
Abstract Author Index
LB59
Abstract Author Disclosure Information
LB66
scientificsessions.diabetes.org
Acute and Chronic Complications
Complications—Hypoglycemia
1-LB
Peripheral GABA Infusion in Diabetic Rats Enhances the Glucagon
Counterregulation and Protects Against Insulin Hypoglycemia
LEON S. FARHY, PATTIE H. HELLMANN, ANTHONY L. MCCALL, Charlottesville,
VA
Glucagon counterregulation (GCR) is often defective in type 1 diabetes (T1DM).
Our animal, clinical, and modeling studies suggest that hyperglucagonemia
contributes to the GCR impairment and alpha-cell inhibitors (ACI) may be
used to improve GCR. This study further supports this hypothesis by showing
that constant peripheral GABA infusion enhances GCR and protects against
hypoglycemia. Blood glucose (BG) and glucagon hypoglycemia responses were
tested in 2 groups of conscious STZ-treated male Wistar rats. BG was lowered
to ~150mg/dL after which a constant (50uL/min) jugular iv infusion of saline
(N=7) or 4mg/mL of GABA (N=9) started (t=-10 min). At t=0 min, a 12U/kg iv
insulin bolus was given. Blood sampling was done every 10min for BG and
glucagon from t= -10 to 80 min. GCR was estimated via the product R={mean
of 2 lowest BG values from t=10 to 40 min} x {mean glucagon from t= 50 to
80 min}. R measures the BG level-specific GCR with higher values indicating a
better response. This design was chosen over a glucose clamp to avoid overinsulinization at the time of GCR. Even though the initial (t< 20 min) glucagon
fold change relative to the basal was lower with GABA vs. saline (meanВ±SD)
(0.9В±0.28 vs. 1.4В±0.54, p=0.04), the later (after t=50 min) BG level-specific GCR
was 72% higher in the GABA group: 3159В±900.5 vs. 2273В±690.4, p=0.04. The
GABA treated group was also better protected against hypoglycemia assessed
by the two lowest BG values after the insulin bolus: 68В±6.5 md/dL vs. 57В±9.5
mg/dL; p=0.02. These results are predicted by our mathematical GCR model in
which reduction of basal glucagon by ACI enhances the defective GCR. They
differ from prior animal work where ACI were given intrapancreatically and
switched off at hypoglycemia. Thus, for the first time GCR enhancement is
achieved by peripheral ACI infusion without a switch-off or other manipulation.
Such treatment could lead to novel strategies for glycemia control in T1DM
with enhanced protection against hypoglycemia.
Supported by: Boehringer Ingelheim Pharmaceuticals, Inc.
3-LB
The Effects of Diabetes Duration on Hypoglycemia Symptom Intensity
and Prevalence of Impaired Awareness of Hypoglycemia
SANDRA E. OLSEN, BJ�RN OLAV ÅSVOLD, BRIAN M. FRIER, SILJE A. EGGEN,
LIZ-IREN HANSEN, MARIT R. BJ�RGAAS, Trondheim, Norway, Edinburgh, United
Kingdom
Diabetes duration influences hypoglycemia symptom profile and prevalence
of impaired awareness of hypoglycemia (IAH); viz. a diminished ability to
perceive onset of hypoglycemia. By questionnaire, hypoglycemia symptoms
and prevalence of IAH were assessed in an outpatient population with type 1
diabetes. Symptom presence and intensity were measured by the Edinburgh
Hypoglycaemia Scale, using a Likert scale of 1 to 7. Hypoglycemia awareness
was assessed by the method of Gold et al., based on the question “do you
know when your hypos are commencing?”, using a scale from 1 to 7 (1 =
always aware, 7 = never aware; ≥ 4 = IAH, < 4 = normal awareness (NAH)).
The response rate was 70% (445/636). IAH was present in 17% (CI: 14-21%).
With progressive diabetes duration, the prevalence of IAH increased (from
3 % for duration 2-9 years to 28 % for duration ≥ 30 years, p for trend <
0.001), the mean intensity of autonomic (A) symptoms declined (p for trend <
0.001) (Fig.1), the intensity of trembling and hunger decreased (p < 0.001 and
p = 0.004, respectively), while the mean intensity of neuroglycopenic (NG)
symptoms did not change (p = 0.55). The mean (SD) ratio of NG/A symptoms
was higher in IAH than in NAH subjects (1.16 (0.43) vs. 1.01 (0.33), p = 0.001).
In conclusion, with progressive diabetes duration, the prevalence of IAH rises
and the intensity of autonomic symptoms, particularly trembling, declines.
Neuroglycopenic symptoms predominated in those with IAH.
Supported by: NIH (RO1DK082805)
2-LB
Lower Risk of Hypoglycemia in Elderly Type 2 Diabetes Patients when
Linagliptin is Added to Basal Insulin: An Exploratory Analysis
SILVIO E. INZUCCHI, MICHAEL NAUCK, MAXIMILIAN VON EYNATTEN, UWE
HEHNKE, HANS-JUERGEN WOERLE, ROBERT R. HENRY, New Haven, CT, Bad
Lauterberg im Harz, Germany, Ingelheim, Germany, San Diego, CA
Elderly T2DM patients (pts) with long-standing disease often require insulin
(INS) therapy, yet hypoglycemia is a major concern. It has recently been shown
that linagliptin (LINA) added to stable basal INS in elderly T2DM pts reduced
HbA1c by -0.77% vs. placebo (PBO), notably with less hypoglycemia. Here we
further explore hypoglycemia risk in these pts (n=247; meanВ±SD age 74В±4
yrs, HbA1c 8.2В±0.8%) on basal INS (baseline [BL] dose 36В±25 U/day) from
two phase 3 studies of 24 and ≥52 weeks. Odds ratios (OR) for overall and
confirmed hypoglycemia (blood glucose ≤70 mg/dl) were assessed (INS doses
did not change notably). Overall (-37%) and confirmed (-34%) hypoglycemia risk
was lower with LINA vs. PBO (OR 0.63 [95% CI 0.37-1.10] [Fig] and 0.66 [0.361.21], respectively). Significantly less (-59%) confirmed hypoglycemia was
found in LINA pts with mild-moderate BL hyperglycemia (HbA1c 7.5-<9.0%;
OR 0.41 [0.21-0.84]; p=0.014). Similar directional trend in hypoglycemia risk
with LINA vs. PBO was also observed in pts with BL HbA1c <7.5% (overall OR
0.77) and subgroups for glargine, detemir or NPH (overall OR 0.74, 0.59, 0.49,
respectively). Despite significantly reduced HbA1c and no relevant on-trial INS
dose reductions, adding LINA to basal INS appears to decrease hypoglycemia
risk. This trend is in stark contrast to other oral agents when combined
with INS. The biological underpinnings of this phenomenon are unclear but
deserving further study.
Supported by: Norwegian Diabetes Association
For author disclosure information, see page LB66.
ADA-Funded Research
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Acute and Chronic Complications
Complications—Macrovascular—
Atherosclerotic Cardiovascular Disease
and Human Diabetes
Limiting Amylin Aggregation Protects the Heart in Diabetes
6-LB
High Sensitivity Cardiac Troponin I as a Diagnostic Tool for the
Presence of Coronary Artery Disease in Stable Diabetic Patients
ALEXANDRE SEGRE, ANTONIO CASELLA-FILHO, MARILIA SPRANDEL, CELIA
STRUNZ, ALESSANDRA ROGGERIO, ANA CARVALHO, DESIDERIO FAVARATO,
PAULO REZENDE, RAUL CAVALCANTE. MARANHAO, ROBERTO KALIL, JOSE
RAMIRES, WHADY HUEB, SГЈo Paulo, Brazil
4-LB
FLORIN DESPA, SANDA DESPA, KALEENA JACKSON, BACH LE, TODD HARRIS,
HUA DONG, NING LI, NIPAVAN CHIAMVIMONVAT, KENNETH B. MARGULIES,
HEINRICH TAEGTMEYER, BRUCE HAMMOCK, Davis, CA, Philadelphia, PA,
Houston, TX
Introduction: The emergence of several high sensitivity troponin (hsTroponin)
assays has shown that cardiac troponins can be chronically elevated in
response to cardiovascular comorbidities. In the absence of unstable coronary
artery disease, pathophysiological mechanisms as increased demand ischemia
or disturbances of cell membrane integrity are possible causes for troponin
leakage. We hypothesized that with a high sensitivity assay, troponin levels
would be higher in diabetic patients with coronary artery disease (CAD), in
comparison to diabetic patients without coronary artery disease.
Objective: To evaluate hsTroponin levels in ambulatory diabetic patients
with multivessel CAD and diabetic patients with angiographically normal
coronary arteries.
Methods: hsTroponin levels were determinated in 85 diabetic patients: 51
women (22 with CAD and 29 with normal coronary arteries) and 44 men (34
with CAD and 10 with normal coronary arteries). Patients were paired by age
and body mass index. Both groups of patients had preserved left ventricular
function measured by ventriculography or echocardiography.
Results: hsTroponin levels were significantly higher (p=0.0005) in diabetic
women with CAD (average = 12.95+5.55 pg/mL) in comparison to diabetic
women with normal coronary arteries (average = 8.02+2.62 pg/mL). hs
Troponin levels were also significantly higher (p=0.0086) in diabetic men with
CAD (average=10.60+4.39 pg/mL) in comparison to diabetic men with normal
coronary arteries (average=6.94+1.67). At a troponin cutoff of 11 pg/mL 90%
of diabetic men and 75% of diabetic women had CAD.
Conclusion: In this study hs Troponin I was a strong marker of CAD in
diabetic patients with multivessel CAD in comparison with diabetic patients
with angiographically normal coronary arteries. hsTroponin may be a useful
tool to stratify the risk of CAD among diabetic patients with normal ventricular
function. The discriminating power was higher among men.
Recent data revealed that the islet amyloid polypeptide (IAPP; amylin), an
amyloidogenic protein making up the pancreatic amyloid in type-2 diabetes
mellitus (T2DM), also accumulates in failing hearts from obese or T2DM
patients. Cardiac deposition of amylin accelerates diabetic heart failure in
a T2DM rat model transgenic for human amylin (the HIP rat). In this study,
we assessed the attachment/incorporation of oligomerized amylin to cardiac
cells in humans and tested the ability of pro-fibrinolytic eicosanoic acids to
reduce amylin deposition and its deleterious cardiac effects in HIP rats.
Oligomerized amylin was identified within coronary arteries, cardiac myocytes
and atherosclerotic lesions in failing hearts from diabetic humans, but not in
control hearts. Intriguingly, significant amylin deposition was found in cardiac
cells from patients that developed T2DM post-transplantation, suggesting
that amylin builds up in the heart and may affect myocardial structure and
function even in pre-diabetes. To elevate the blood level of eicosanoids and
block cardiac amylin deposition in HIP rats, we treated animals in pre-diabetic
state with an inhibitor of soluble epoxide hydrolase, the enzyme that degrades
endogenous eicosanoids. Treatment doubled the blood concentration of profibrinolytic eicosanoids, which drastically limited the attachment/incorporation
of oligomerized amylin to cardiac myocytes. Animals in the treated group
displayed reduced cardiac hypertrophy and left-ventricular dilation. We show
that possible cardioprotective effects include limiting amylin-induced cardiac
oxidative stress and myocyte Ca2+ cycling alteration. The present studies
point to cardiac amylin accumulation as a novel therapeutic target in diabetic
heart disease and elevating the blood level of pro-fibrinolytic molecules as
a pharmacological strategy to reduce amylin deposition and amylin-mediated
cardiotoxicity.
Supported by: NSF-CBET 1133339
Complications—Nephropathy—Basic and
Experimental Science
5-LB
Blood Pressure and Vascular Function in Sprague-Dawley Rats With
Insulin-Treated Type I Diabetes Mellitus
7-LB
The Regulation of PPAR-Оі on TGF-ОІ1 and c-Ski in Kidney Tissue of
Diabetic Rats
DYLAN OLVER, KENNETH N. GRISÉ, MATTHEW W. MCDONALD, ADWITIA
DEY, ANDREW W. COLLINS, EARL G. NOBLE, JAMIE W.J. MELLING, KEVIN
SHOEMAKER, London, ON, Canada
DE MIN LIU, Tianjin, China
TGF-ОІ1 is the critical cytokine of glomerulosclerosis and renal interstitial
fibrosis. As the repressor of TGF-ОІ/Smad pathway, c-Ski could inhibit the
Smad compound activating the transcription of its downstream target gene.
In this study, the diabetic models were induced with streptozotocin, and
some of them were treated with Pioglitazone. We observed the expressions
of c-Ski and TGF-ОІ1 in renal tissue of diabetic rats, to investigate their
relationship with diabetic nephropathy and the effect of PPAR-Оі on TGF-ОІ1
and c-Ski. All the SD rats were randomized into normal control group (NC),
diabetes group (DM) and treatment group (PT). The body mass weight was
measured every week, and the level of blood glucose was measured every
two weeks. All the indicators related to renal function such as blood urea
nitrogen (BUN), Triglyceride (TG), 24h urinary microalbumin (UMA) and kidney
hypertrophy index (LKW/BWT) were detected in rats sacrificed after 8 weeks
of experiment. The 24 hour urine of all the rats were collected one day before
they died. All the nephridial tissues underwent hematoxylin and eosin stain to
observe pathological morphology of nephridial tissues. The protein levels of
TGF-ОІ1 and c-Ski were determined by immunohistochemistry. Compared with
NC group, the levels of 24h urinary volume, 24h UMA, BUN, TG, LKW/BWT and
TGF-ОІ1 were significantly higher (P<0.01) , while c-Ski was significantly lower
in the DM group(P<0.01). After treatment with Pioglitazone, all the related
biochemical data and TGF-ОІ1 decreased (P<0.05), while c-Ski was higher
(P<0.01). In conclusion , Pioglitazone could significantly up-regulate protein
level of c-Ski and inhibit TGF-ОІ1 in kidney tissue of diabetic rats, which may
play an important role in ameliorating the process of diabetic nephropathy.
The purpose of this study was to determine if insulin-treated type I diabetes
mellitus (T1DM) altered conscious resting blood pressure (BP) through a
NO mechanism in Sprague-Dawley rats. Rats were divided into 2 groups,
control (C) and TIDM (daily streptozotocin injections of 20 mg/kg for 5 days;
followed by a subcutaneous insulin pellet implant: 1 IU/12 h; fed state blood
glucose ~16 mmol/L). Resting conscious BP and the BP response to L-NGMonomethylarginine (L-NMMA; 30 mg/kg) infusion was measured at week 1
and week 10 following insulin therapy. At week 11, rats were anaesthetized,
the right jugular vein was cannulated for acetylcholine (ACh; 25 ug/kg) and
prazosin (PRZ; 85 ug/kg) infusions and the right carotid artery was cannulated
for continuous BP measurement. Following the experiment, femoral arteries
(FA) were harvested for tissues analyses. At week 1, conscious BP (C=109В±12
vs. T1DM=109В±6 mmHg) and the increase in BP (~20%) following L-NMMA was
the same (P≤0.72) between groups. At week 10, rats with T1DM had higher
resting BP (T1DM=147В±5 vs. C=113В±7; P<0.01). The BP response to L-NMMA
was preserved in C (P<0.01) but not T1DM (P=0.86) rats. Under anaesthetia,
BP reductions (~45 mmHg) to systemic ACh infusions were similar (P=0.78)
between groups. However, in rats with T1DM, reductions in BP following PRZ
infusion were greater (T1DM=49В±22 vs. C=17В±18 mmHg; P=0.02) and basal
NPY concentrations were greater (T1DM=718В±118 vs. C=517В±91; P<0.01). FA
endothelial NO synthase content was similar (T1DM=0.95В±0.04 vs. C=0.92В±0.06
eNOS/ОІ-actin; P=0.21) between groups. However, in rats with T1DM the cross
sectional area of FA smooth muscle was greater (T1DM1=142В±55 vs. C=96В±6
Вµm2; P=0.05). These data suggest a role for impaired NO function, sympathetic
hyperactivity and/or smooth muscle hypertrophy in the etiology of T1DM
related hypertension.
Supported by: CIHR
For author disclosure information, see page LB66.
ADA-Funded Research
LB2
Acute and Chronic Complications
Complications—Nephropathy—Clinical and
Translational Research
8-LB
Blood Pressure and Pulse Pressure Effects on Renal Outcomes in the
Veterans Affairs Diabetes Trial (VADT)
ROBERT J. ANDERSON, GIDEON BAHN, NICHOLAS EMANUELE, JENNIFER
MARKS, WILLIAM DUCKWORTH, Omaha, NE, Hines, IL, Miami, FL, Phoenix, AZ
The Veterans Affairs Diabetes Trial (VADT) was a prospective, randomized
study of 1791 veterans with T2DM. The primary goal was to determine
whether intensive glucose control prevented major cardiovascular disease
events. Our current objective was to determine whether on study systolic blood
pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) affected
renal outcomes measured as albumin creatinine ratio (ACR) and estimated
glomerular filtration rate (eGFR) evaluated by time-varying covariates survival
analyses and hazard ratios (HR) for worsening of renal outcomes.
Compared with SBP 105-129 mmHg, the risk of ACR worsening increased
significantly for SBP 130-139 mmHg (HR=1.879; 95% CI=1.276-2.769; P=0.001),
and for SBP ≥140 mmHg (HR=2.506; CI=1.663-3.776; P<0.0001). A1c as a timevarying covariate also increased risk of ACR worsening (HR=1.194; CI=1.0891.309; P=0.0002). Compared with a PP range of 40-49 mmHg, PP<40 significantly
lowered risk of worsening ACR (HR=0.364; CI=0.153-0.865; P=0.022), and PP>60
significantly increased risk (HR=2.382; CI=1.579-3.593; P<0.0001). Analyses of
categorical BP ranges associated with eGFR worsening showed a significant
interaction between patients with SBP≥140 mmHg and A1c. Compared with
the SBP 105-129 mmHg group, patients with SBP≥140 mmHg were 15% more
likely to experience eGFR worsening (HR=1.149; CI=1.003-1.317, P=0.045) for
each 1% A1c increase. We conclude that SBP ≥130 mmHg, higher A1c and
PP>60 were associated with worsening ACR. PP<40 showed a lower risk for
worsening ACR. The results suggest that treatment of SBP to below 130 mmHg
may lessen ACR worsening. In light of the interaction effect between SBP≥140
mmHg and A1c, our results suggest that the effect of glycemic control on
reducing progression of renal disease may be even greater in hypertensive
patients.
10-LB
Small Particle Diet Reduces Upper Gastrointestinal (GI) Symptoms in
Patients With Diabetic Gastroparesis: A Randomized Controlled Trial
EVA A. OLAUSSON, STINE STORSRUD, STIG ATTVALL, MAGNUS SIMRÉN,
Gothenburg, Sweden
Gastroparesis is a complication to diabetes mellitus (DM). The prevalence
is suggested to be 30- 65%. Dietary advice is considered to be of importance
to reduce GI symptoms in patients with diabetic gastroparesis (GP), but no
randomized controlled trials exist.
Our aim was to compare GI symptoms in insulin treated DM subjects with
GP eating a food with small particle size (“intervention diet”), compared with
the recommended diet for DM (“control diet”).
We randomized 56 subjects with insulin treated DM and GP (mean 53.3 В±
11.6 years age; 35 females), determined with scintigraphy, to the intervention
diet or to the control diet for 20 weeks. The patients met a dietitian at 7
occasions during the study. GI symptom severity was assessed with a validated
questionnaire, (PAGI-SYM). BMI and HbA1c were followed.
A significantly greater reduction of nausea/vomiting, postprandial fullness,
bloating, and regurgitation/heartburn were seen in patients who received the
intervention diet compared with the control diet, but not for abdominal pain
(see table). No differences in BMI and HbA1c were seen between the groups.
The authorВґs conclusion: A dietary treatment with small particle size
significantly improves the key symptoms of gastroparesis in patients with
diabetes mellitus.
Supported by: U.S. Dept. of Veterans Affairs
Complications—Neuropathy
9-LB
Effect of Aerobic Exercise on Quality of Life of Individuals With Diabetic
Peripheral Neuropathy: A Single Blind, Randomized Controlled Trial
SNEHIL DIXIT, Manipal, India
The objective of the study was to evaluate the effect of moderate
intensity (Heart Rate Reserve 40-60%) exercise on Neuropathy Quality of
life (NQOL) in type 2 diabetes. The study was a parallel-group, randomized
clinical trial performed in a tertiary setting. People with type 2 diabetes with
clinical neuropathy were included if they had a minimum score of 7 on the
Michigan Diabetic Neuropathy Score (MDNS). Following which the patients
were randomly assigned to intervention or standard care for eight weeks.
RANOVA was used for data analysis and p < 0.05 was considered significant.
After randomization there were 47 participants in the control group and 40
participants in the exercise group. The results showed a significant difference
in mean scores of two groups for MDNS and NQOL post intervention.The two
groups had a significant difference for pain scores with F = 6.7 and p =0.01,
sensory symptom scores had F =4.60 and p = 0.04, restricted activities of daily
living had F =4.97 and p =0.03, disruptions in social relationships score had
a F =5.43 and p = 0.02, specific impact on quality of life score had F = 9.28
and p = 0.00 and overall quality of life score had a F =28.72 and p = 0.00 and
total score for NQOL had F = 31.10 and p = 0.00. Degrees of freedom for all
the components were 1,62. In conclusion moderate intensity aerobic exercises
helps to improve the NQOL of individuals with peripheral neuropathy in type
2 diabetes.
For author disclosure information, see page LB66.
ADA-Funded Research
LB3
Acute and Chronic Complications
11-LB
13-LB
Intermittent Fasting (IF) at Night Protects from Diabetic Microvascular
Complications in db/db Mice
Relationship of Visceral and Subcutaneous Adiposity With the Severity
of DM Retinopathy in People With Type 2 Diabetes Mellitus
YUANQING YAN, TATIANA SALAZAR, ASHAY D. BHATWADEKAR, JAMES
DOMINGUEZ, DUNG NGUYEN, REHAE MILLER, MICHAEL E. BOULTON, JULIA V.
BUSIK, MARIA B. GRANT, Gainesville, FL, Ann Arbor, MI
HO RA, YONG KYUN KIM, Bucheon-si, Geoynggi-do, Republic of Korea
Our study was performed to determine whether Visceral adiposity (VAT)
or subcutaneous adiposity (SAT) was associated with the severity of DM
retinopathy in people with type 2 DM. Nine hundred and twenty-nine people
with type 2 DM and who had undergone abdominal computed tomography
assessment of the SAT and VAT areas were included. the severity of DM
retinopathy graded to 9 categories(no retinopathy, microaneurysms only, mild
NPDR, mod NPDR, severe NPDR, very severe NPDR, PDR without HRC, PDR
with HRC, advanced PDR). VAT was positively associated with the severity
of DM retinopathy after adjustment for the clinical variables (ОІ-coefficient
=0.085, P = 0.034), while SAT was not significantly associated with the severity
of DM retinopathy. When stratifying the individuals by the body mass index
groups, VAT was positively associated with severity of DM retinopathy in the
overweight and obese subjects after adjustment for the clinical variables,
while there was no significant association between the VAT and the severity
of DM retinopathy in the normal weight subjects. SAT was not significantly
associated with severity of DM retinopathy in the normal weight, overweight
and obese subjects Our data suggest that VAT may be an additional prognostic
factor for the severity of DM retinopathy especially in the overweight or obese
subjects with type 2 DM.
Previously, we identified that diabetic bone marrow (BM) neuropathy
precedes diabetic retinopathy (DR) (Busik et al. 2009) and circadian
dysregulation of vascular progenitors (VP) profoundly contribute towards
retinal vascular dysfunction. This study explored whether correction of
diurnal dysfunction and restoration of VP function is a strategy for prevention
microvascular complications.
db/db and age match control (db/m) mice were maintained under a 12h:
12h/light: dark cycle for six months starting at 4 month of age with either
normal feeding or with IF, initiated at night time every other day with food
(normal chow) introduced 5~30min before lights were off on the first day and
removed 5~30min before the lights were off on the second day. At study end,
mice were euthanized every 4 hrs for 48hrs. Glycated hemoglobin (GlyH), VP
enumeration in BM and blood (by flow cytometry), VP migration (by QCM
Chemotaxis Assay) and circadian clock gene expression, BMAL and PER2, (by
RT-PCR), NF200 staining in BM for neuropathy assessment and enumeration of
acellular capillaries was performed.
In db/db mice under ad libitum feeding marked dysfunction was observed:
i) loss of diurnal oscillation of BMAL and PER2 mRNA expression in BM VP;
ii) increase in BM VP numbers iii) reduced VP migration; and iv) DR and DN
development. Without changing levels of GlyH, IF initiated at night time
increased the survival rate in db/db mice, corrected diurnal disruption of VP
release from BM and diurnal oscillation of BMAL and PER2 gene expression,
restored VP migration to normal nondiabetic levels. IF of db/db mice prevented
development of diabetic neuropathy as assessed by NF200 staining in BM and
DR as assesses by the number of acellular capillaries.
Our results suggest that by simply changing the timing of food consumption,
circadian dysregulation can be corrected and diabetic microvascular
complications prevented without improving GlyH levels.
14-LB
The Association of HbA1c (Long-Term Hyperglycemia) With the Risk of
Pulmonary Embolism (PE)
SE MIN KIM, JONGOH KIM, ARTHUR CHERNOFF, Philadelphia, PA, Houston, TX
Background: Diabetes mellitus is well-known pro-thrombotic condition.
Hyperglycemia is associated with arterial thrombosis, and also has shown
increased risk of venous thrombosis. The objective of this study is to evaluate
the association of long-term hyperglycemia with the risk of pulmonary
embolism.
Methods: We conducted a retrospective, case- control study that reviewed
patients who were admitted to Albert Einstein Medical Center from 2005 to
2011. The case group was 140 patients with confirmed pulmonary embolism
by diagnostic study (positive CT chest w/ contrast or high probability with V/Q
scan) during the period. Controls were selected age-, sex- matched, in a 1:2
ratio from individuals who had negative diagnostic studies for PE during the
same period. Those who had HbA1c values measured during the admission
were included. Patients who were on anticoagulation at the time of admission
for any reason were excluded. Logistic regression was used for statistical
analysis.
Results: The mean age of the study population was 64. 60% of the patients
were women, and 71% were African American. The prevalence of diabetes
was not different in two groups (65.0% vs. 72.3%, p=0.125). However, HbA1c
was statistically significantly higher in the case group than in the control group
(7.53% vs. 7.09%, p=0.012). The unadjusted odds ratio of PE with respect to
HbA1c was 1.16 (CI 95%, 1.03-1.30). Multi-logistic regression adjusted for
demographics and known risk factors for PE such as immobilization, recent
surgery, malignancy and history of venous thromboembolism also yielded odds
ratio of 1.28 (CI 95%, 1.09-1.50). When stratified by status of diabetes, the
adjusted odds ratio was 1.06 (CI 95%, 0.76-1.49) in non-diabetes and 1.38(CI
95%, 1.17-1.62) in diabetes.
Conclusion: The study suggests that long-term hyperglycemia, particularly
in those with diabetes, is associated with a significant risk of pulmonary
embolism.
Supported by: R01DK090730, R01EY007739
Complications—Ocular
12-LB
Histone Methyltransferase EZH2 Regulates Glucose Induced VEGF
Production through H3K27 Methylation in Retinal Endothelial Cells
MICHAEL A. RUIZ, SUBRATA CHAKRABARTI, London, ON, Canada
Glucose induced augmented vascular endothelial growth factor (VEGF)
production is a key event in diabetic retinopathy. We have previously
demonstrated that downregulation of miR-200b causes overexpression of
VEGF, mediating structural and functional changes in the retina in diabetes
(Diabetes 60:1314,2011). However, regulation of miR-200b is not known.
Histone methyltransferase, enhancer of the zeste homolog (EZH2), has been
demonstrated to repress miRNAs in neoplastic process. We hypothesized that,
in diabetes, EZH2 represses miR-200b through its H3K27 methylation mark.
Human endothelial cells of dermal origin, isolated from both type 1 and type
2 diabetic and non-diabetic individuals, and retinal microvascular endothelial
cells were treated in high glucose (25mM) or normal glucose (5mM) for 24
hours. Expression of EZH2, VEGF and various miRNA were measured by qPCR.
Loss-of-function experiments were also performed using a chemical inhibitor
for EZH2, 3-Deazaneplanocin A (DZNep).
When treated with high glucose, all cell types showed significantly increased
VEGF expression. Retinal endothelial cells showed increased expression
of EZH2 with decreased expression of miR-200b. Dermal endothelial cells
isolated from diabetic patients showed increased EZH2 and decreased miR200b expression as well. Furthermore, inhibition of EZH2 in retinal endothelial
cells produced increased miR-200b expression with parallel decreased VEGF,
demonstrating a causal link.
This research has demonstrated a repressive relationship between EZH2
and miR-200b. These data further provide evidence of a novel mechanism of
miRNA regulation through another epigenetic pathway, i.e, histone methylation.
Understanding such pathways will potentially yield new treatment strategies.
15-LB
Imbalance in NGF/proNGF Ratio as Biomarker of Diabetic RetinoВ­
pathy
AZZA B. EL-REMESSY, ABDELRAHMAN FOUDA, AMINA FAROOQ, ISLAM
N. MOHAMED, BARBARA A. MYSONA, SURAPORN MATRAGOON, DEIGO
ESPINOSA-HEIDMANN, Augusta, GA
Background: Our previous studies have demonstrated that diabetes-induced
oxidative stress can alter the homeostasis of retinal nerve growth factor (NGF)
resulting in accumulation of its precursor, proNGF at the expense of NGF. This
imbalance coincided with retinal damage in experimental diabetes. Here
we test the hypothesis that alteration of NGF and proNGF levels observed
in retina and ocular fluids will be mirrored in experimental and clinical
diabetes. Methods: Blood and vitreous samples were collected from patients
undergoing vitreoctomy at Georgia Reagents University under approved
IRB. Samples included patients with diabetic retinopathy and non- diabetic
(controls). Western Blot analysis was performed on serum samples collected
Supported by: CDA; CIHR
For author disclosure information, see page LB66.
ADA-Funded Research
LB4
Acute and Chronic Complications
from diabetic and non-diabetic patients as well as samples (retina and serum)
collected from C57Bl/6 mice that were kept diabetic for 5- weeks using STZmodel. Results: Diabetes significantly increased proNGF levels to 2.25 fold of
the control levels in both retina and plasma of the same STZ-mice (n=4-5).
NGF expression was markedly attenuated in diabetic mice to 50% and 60%
in retina and plasma of the same animals, respectively. In human samples,
vitreous and sera from diabetic patients showed 3-fold and 1.4-fold increase,
respectively compared to non-diabetic (n=4-6). Vitreous and sera from
diabetic patients showed significant 40% and 50% reduction in NGF levels,
respectively when compared to non-diabetics. Conclusion: Our results showed
that diabetes-induced expression of proNGF and impaired NGF expression
was comparable between ocular fluid and serum. NGF plays an important role
in improved wound healing, inflammatory responses, and preserving retinal
function. Further characterization of the imbalance of proNGF to NGF ratio may
facilitate its utility as an earlier biomarker for diabetic complication including
diabetic retinopathy.
17-LB
Protecting Retinal Pigment Epithelium and the Outer Blood-Retinal
Barrier: Role of X-Box Binding Protein 1
JIANXIN WANG, CHEN CHEN, YIMIN ZHONG, SARAH XIN ZHANG, Buffalo, NY
Normal function of the retinal pigment epithelium (RPE) is essential for
maintaining integrity of the outer blood-retinal barrier (BRB). Oxidative injury of
the RPE resulting in disturbance in RPE tight junctions is implicated in diabetic
retinopathy. The transcription factor NF-E2-related factor2 (Nrf2) is a central
regulator of cellular antioxidant responses. Enhancing Nrf2 activity protects
RPE cells from oxidative injury, and recent studies suggest an important role
of Nrf2 in regulation of epidermal barrier function. In the present study, we
examined the role of X box-binding protein 1 (XBP1), an ER stress-inducible
transcription factor, in regulation of Nrf2 and tight junctions in the RPE. Our
results show that in RPE-specific XBP1 knockout (KO) mice, Nrf2 level in the RPE
was significantly lower compared to wildtype (WT) mice Expressions of Nrf2
target genes were also decreased in XBP1-deficient RPE. Confocal microscopy
of RPE flatmount shows disturbed tight junctions between RPE cells in XBP1deficient mice. In line with the in vivo findings, primary RPE cells isolated
from XBP1 KO mice expressed less Nrf2 than those from WT mice. In cultured
human RPE cells, overexpressing XBP1 increased Nrf2 level, while knockdown
of XBP1 by siRNA or inhibiting XBP1 splicing resulted in a decrease in Nrf2 and
disruption in tight junction formation. Moreover, induction of XBP1 splicing by
tunicamycin and thapsigargin increased Nrf2 expression, while quinotrierixin,
a XBP1 splicing inhibitor, abolished tunicamycin- and thapsigargin-induced
Nrf2 upregulation. Taken together, our results indicate that XBP1 is required for
Nrf2 expression in RPE cells and that deficiency of XBP1 resulting in decreased
anti-oxidant response contributes to oxidative injury and tight junction damage
of the RPE.
Supported by: JDRF; RO1EY042208; University of Georgia
16-LB
Plasma Biomarkers For Diabetic Retinopathy Discovered Using
SOMAscanв„ў
ALEX STEWART, BRITTA SINGER, ROBERT E. MEHLER, ANTONIO CIARDELLA,
TIM BAUER, STEPHEN WILLIAMS, Boulder, CO, Denver, CO
A blood test that provides a timely and accurate diagnosis of diabetic
retinopathy (DR), especially in the 50% of diabetic subjects not adherent to
eye exams, could be used to drive preventive interventions. A prospective
case-control study enrolled 88 diabetic subjects. Blood samples were collected
just before an eye examination by an ophthalmologist. Thirty-five (35) subjects
had DR and 53 had no evidence of DR. Of the subjects with DR, 5 had Grade
1, 12 Grade 2, 9 Grade 3, 5 Grade 4, and 4 Grade 5. The 88 plasma samples
were run on SOMAscan™, SomaLogic’s SOMAmer-based proteomic assay
that identifies and quantifies over a thousand proteins across approximately
eight logs of concentration in small sample volumes. Sixteen proteins were
significantly related to the presence of retinopathy, and were used to construct
random forests classifiers to distinguish patients with DR from those with no
DR. Peak performance was achieved by a 7-protein classifier which displayed
sensitivity of 0.74, specificity of 0.89, and AUC of 0.92. For several proteins the
concentration related to the stage of DR. The biologic classifications of the 7
proteins included inflammatory, neuron-derived, and cardiovascular. We are
planning validation studies.
Supported by: NIH (EY019949)
Diabetic Dyslipidemia
18-LB
Safe and Selective Small Molecule RxRО± Agonist Modulates Glucose
and Lipid Metabolism in ob/ob Mice
M.R. JAGANNATH, B.P. SOMESH, M.V. VENKATARANGANNA, O. ANUP, S.
MANOВ­В­JKUMAR, D. ANILKUMAR, YOGANAND MOOLEMATH, R. MADHUSUDAN,
ASHOK R. KUMAR, JAIDEEP SINGH, V. SUNIL, Bangalore, India
Retinoid X Receptor О± (RXRО±) regulates intracellular receptor signaling
pathways involved in, among others, glucose and lipid metabolism and
has potential to impact multiple risk factors associated with the metabolic
syndrome. In the present study we investigated the effect of a potent and
selective RXRО± agonist CNX-013-B2 (30 mg/kg, p.o., BID for 4 weeks) in
obese-hyperglycemic ob/ob mice.
Treatment with CNX-013-B2 did not increase either food intake or body
weight. In comparison with control ob/ob animals treatment with CNX-013-B2
resulted in a 22% reduction in fed glucose (196.30В±3.16 Vs. 153В±3.83 mg/
dl), 16% in fasting serum triglycerides (141.85В±8 Vs. 119В±3 mg/dl), 20% free
fatty acids, 14% fasting glycerol, 14% cholesterol and 26% LDL (low-density
lipoprotein). In an oral glucose tolerance test a 19% decrease in glucose
AUC was observed in the agonist treated animals indicating improvement in
insulin sensitivity. After 4 weeks there was no significant change in weight
of different depots of fat, kidney and pancreas. A non-significant increase in
liver weight was observed in treated animals. In muscle expression of PDK4,
SREBP1c, UCP3 and ABCA1 was significantly increased suggesting enhanced
glucose and fat metabolism. In liver increased expression of SREBP1c, FASN
and SCD1 suggested enhanced de novo lipogenesis. However the increase in
liver triglyceride accumulation was non-significant (7%). Expression levels of
Cyp7A1, bile acid transporters like MDR3, MRP4 and NTCP and cholesterol
transport genes like ABCG5 suggest a robust modulation of cholesterol
metabolism in treated animals. Gene expression profile in inguinal fat (PPARОі,
UCP2, SREBP1c) indicates increased insulin sensitivity. Treatment of C57BL6/j
DIO mice on HFD with 100mg/kg for 5 weeks with CNX_013_B2 did not reduce
serum levels of T3, T4 and TSH which indicates minimal impact on the HPT
axis. CNX-013-B2 is a highly active and selective RXR agonist with good
potential to provide glycemic and lipid control.
For author disclosure information, see page LB66.
ADA-Funded Research
LB5
Acute and Chronic Complications
19-LB
21-LB
Debio 0930, a Novel Direct AMPK Activator, Improves Glycemic Control
and Lipid Profile in Metabolic Disease Models
Existence of a Triglyceride-Dependent Glycemic Regulatory Pathway
in Patients With Type 2 Diabetes
PATRICK MUZZIN, MARIA VON HOLTEY, MARYSE BARBIER, ROBERT LYSEK,
ANDRES MCALLISTER, Lausanne, Switzerland
HAROLD E. LEBOVITZ, METACURE STUDY GROUP, New York, NY
Gastric electrical stimulation by the Tantalus-Diamond device has been
shown to reduce A1C, weight and blood pressure in patients with type 2
diabetes (T2DM) inadequately controlled with oral antidiabetic agents (J
Diabetes Sci Technol 3:964-970, 2009). A proposed mechanism for these
actions is a vagus nerve-mediated CNS pathway. A retrospective analysis
of 40 patients treated with the Tantalus device for at least 12 months has
shown that the improvement in glycemic control is inversely correlated with
the fasting plasma triglyceride (TG) level (Diabetic Med. online Jan. 13,
2013). Studies in rodents have described a gut-brain-liver axis involving upper
intestinal lipids to regulate glucose production (Nature 452:1012-1016, 2008).
In a prospective study, 21 patients with T2DM inadequately controlled on oral
agents who had been implanted with the Tantalus and had completed a 12
month randomized crossover control versus electrical stimulation study were
enrolled into an additional 6 month study in which all had TG measurements
and received electrical stimulation. The goal was to assess the effect of the
TG levels on the A1C levels achieved at the end of the 6 months electrical
stimulation. The mean A1C after 6 months in 9 patients with TG ≤ 1.7 mmol/L
was 7.7 В± 0.43 % which was a 0.92 В± 0.31 % decrease from the baseline
values preceding implantation of the Tantalus. This contrasted to a mean of
8.33 В± 0.45 % in 12 patients with TG >1.7 mmol/L which was a mean increase
from baseline of 0.21 В± 0.36 % (treatment difference 1.23 %, p < 0.05). The
Pearson correlation coefficient for the lnTG versus the change in A1C from
baseline was 0.535 (p = 0.012). These data confirm the previous retrospective
data and are consistent with the rodent data suggesting the existence of a
triglyceride sensitive glucose regulatory pathway in humans.
AMP-activated protein kinase (AMPK), a key cellular energy sensor, is a
promising target for the treatment of metabolic disorders. This study describes
the in vivo metabolic effects of a novel direct AMPK activator, Debio 0930,
which is under preclinical development for type 2 diabetes.
Debio 0930, a small molecule, activated at least two recombinant human
AMPK heterotrimers containing the Гџ1 subunit in a submicromolar range
(5-12 fold stimulation). In human HepG2 hepatocytes, Debio 0930 promoted
AMPK activation without any changes in AMP/ATP ratio, supporting a direct
mechanism of action. Debio 0930 was also found to have attractive DMPK
properties with a favorable in vitro safety profile.
In vivo efficacy of the compound was examined in diet-induced obese (DIO)
mice and dyslipidemic hamsters. Following 4-week oral repeat dosing in the
DIO mice, Debio 0930 at 60 mg/kg BID reduced fasting plasma glucose and
hepatic glucose production, and ameliorated insulin resistance (HOMA-IR).
In addition, the treatment demonstrated marked improvement in liver lipid
content (TG, Chol, FFA). In dyslipidemic hamsters, oral administration of Debio
0930 at 60 mg/kg for two weeks lowered fasting blood glucose and enhanced
the HDL/LDL ratio. Plasma lipoprotein analysis demonstrated that Debio 0930
caused a significant reduction in VLDL and LDL and a substantial rise in HDL
compared to vehicle treated animals. Food intake was not affected by Debio
0930 in either study.
In conclusion, Debio 0930 is a novel direct AMPK activator that improves
both glycemic control and lipid profile, and potentially could be a new oral
agent for the treatment of type 2 diabetes and dyslipidemia.
Supported by: MetaCure
20-LB
Acute Changes in Glucose Metabolism are Linked to Lipoprotein
Alterations, and may Impact Endothelial Health
Foot Care—Lower Extremities
SAHAR S. ABDELMONEIM, AMY K. SAENGER, BRENDA KIRBY, EDWARD
MENDRICK, BARBRA NORBY, TAMARA M. ROBERSON, ANANDA BASU, ALLAN
JAFFE, JAMES OTVOS, SHARON L. MULVAGH, Rochester, MN, Raleigh, NC
22-LB
Withdrawn
We examined the effect of acute hyperglycemia on lipoprotein particle
concentrations utilizing nuclear magnetic resonance (NMR) spectroscopy in
healthy subjects. Baseline endothelial function was evaluated by reactive
hyperemia index (RHI) using Endo-PAT. We studied 9 healthy subjects (8
females, age 46 В± 6 yrs, fasting blood sugar (BS) 5В± 0.3 mmol/l, HbA1C 5 В±
0.3 %) following overnight fast during 2-step pancreatic clamp [somatostatin,
glucagon, insulin (0.75 mU/KgTBW/min)] and GLP-1 (1.2 pmol/kg/min).
Glucose infusions maintained euglycemia (BS 5 В± 0.5 mmol/l), followed by
hyperglycemia (BS 13 В± 0.6 mmol/l) for 2 hrs. Endothelial dysfunction was RHI
<2.0. NMR profile included total NMR protein,total cholesterol, triglycerides,
HDL-C, LDL-C, LDL-p, sLDL-p, HDL-p, and lgHDL-p concentrations and was
evaluated at baseline, euglycemia and hyperglycemia. RHI (mean 2.1 В± 0.6)
was significantly correlated to baseline HDL-p (r = 0.7, p= 0.03), and maintained
significance after adjusting for age (p=0.04). Significant decrease in NMR
fractions during hyperglycemia was observed.
Conclusions: Acute hyperglycemia resulted in a significant decrease in
total and large HDL-p concentrations measured by NMR. HDL-p had a positive
correlation with baseline endothelial function, as determined by RHI. These
observations suggest that acute changes in glucose metabolism are linked to
lipoprotein alterations, and impact endothelial health.
23-LB
Heat Shock Protein 70 (HSP70) Gene Polymorphism: A Risk for Diabetic
Foot Amputation
ANIL KUMAR, S.K. GUPTA, ASHOK KUMAR, S.K. SINGH, Varanasi, India
Heat shock protein (HSP) has been identified playing role in repair of damaged
tissue. It might have role in impaired diabetic wound healing also. Present
study was designed to assess HSP gene polymorphism and it association with
severity and prognosis of diabetic foot ulcer.
Venous blood was taken from 50 patients with diabetic foot. DNA was
extracted and HSP A1B/ HSPA1L genes were amplified by PCR using specific
primers. Following enzyme (restriction endonucleases PstI and NcoI ) digestion
of the amplicons, RFLP analysis was done by gel electrophoresis.
HPS A1 B polymorphism was identified as AG in 82%, GG in 18% and GG
in none of the patients with diabetic foot ulcer.HPS A1 L gene polymorphism
was identified as TT in 80% , CT in 18 % and CC in 2 % of the patients.
AG polymorphic variant HPS A1L and TT polymorphic variant HPS A1B
was associated with severe wound grade (Wagner’s 3, 4 and 5) and risk
of amputation. Other polymorphic variants of HPSA1L/HPSA1B genes did
not show such association. HPS A1B and HPSA1B genes (encoding HPS 70
protein) polymorphism was associated with severity of diabetic foot ulcer. AG
and TT Polymorphic variant of HPS A1B and HPSA1L genes increased the risk
of amputation of diabetic foot. The study thus suggested role of quantitative
proteomic analysis of HPS 70 as a prognostic marker of diabetic foot
Table. NMR Fractions During Glycemic Stages (Values expressed as mean
В± SD)
NMR fraction
Euglycemia Hyperglycemia
P
stage
stage
value
NMR protein, ng/mL
466.1 В± 39.4
436.1В±31.9
0.0003
Total cholesterol , mg/dL
147.6 В± 24.5 135.7 В± 22.4 0.0004
Triglycerides , mg/dL
77.6 В± 27.8
55.1 В± 20.3 <0.0001
LDL cholesterol (LDL-C),mg/dL
81.8В± 19.1
79.4 В± 18.7 0.224
HDL cholesterol (HDL-C),mg/dL
49.9 В± 7.6
45.9 В± 7.6
0.0014
Total LDL particles (LDL-p),nmol/L
902.4 В± 359
860.7 В± 334.0 0.192
LDLp size (nm)
21.3 В±1.09
21.3В±1.06
0.681
Total small LDL particles (sLDL-p), nmol/L
601.0 В±345.1 593.1 В± 350.2 0.772
Mean HDLp size (nm)
9.1 В± 0.48
9.1 В±0.51
0.104
Total total HDL particles (HDL-p), Ојmol/L
30.4 В± 4.79
28.7 В± 4.8
0.002
Large HDL p(lgHDL-), Ојmol/L
7.86 В± 2.67
7.17 В± 2.53 0.032
Supported by: NIH (UL1TR000135)
For author disclosure information, see page LB66.
ADA-Funded Research
LB6
Behavioral Medicine, Clinical Nutrition, Education, and Exercise
Diabetes Education
24-LB
Safe Use of Non Insulin Therapies e-Learning—Module Evaluation
JUNE R. JAMES, HEATHER STEPHENS, LOUISE RICHARDS, GRACE SWEENEY,
HELEN WILKINSON, ANNA MORTON, Leicester, United Kingdom, Newcastle upon
Tyne, United Kingdom, London, United Kingdom
A “safe use of non-insulin therapies” e-learning module aimed at reducing
medication error by hospital and community staff launched in August 2012,
was evaluated by learners in March 2013.
The aims were to review the impact of module completion on individuals’
confidence and practice. 2747 (31.3%) of 8813 had completed training by
1/3/2013. Those completing Sept - Nov 2012 were asked to complete an
on-line survey comprising of 11 questions previously pilot tested. This tool
combined both quantitative and qualitative data collection.
Data was collected from 191 (17.4%) staff, 65.4%, n=125 (nurses), 14.1%
n=27 (doctors), 20.4%, n=39 others.
69.6%, n=133 participated for CPD, for 34% n=65, it was mandated, 16.2%
n=31 were advised to complete by a manager. Other reasons (12.6% n=24)
included; assessing for others, personal interest, compulsory element within
another course.
Increased confidence with non-insulin therapies reported as a result of
course completion were in:
Supported by: Bowes Fund
26-LB
Development and Validation of a Carbohydrate and Insulin Dosing
Knowledge Quiz in Asian Patients With Diabetes Mellitus on Prandial
Insulin
•Managing (127/188, 67.5%)
•Administering (110/180,61.1%)
•Prescribing (59/150,39.3%)
ANGELA KOH, ANURADHA NEGI, MEE LI YAP, PEI LING KOH, CHEE FANG SUM,
Singapore, Singapore
86 (45%) reported changes in working practice, 44% (n=84) no changes,
11% (n=21) unsure. Changes were reported in management (37.7%, n=72),
administration (20.9%, n=40) and prescribing (12.6%, n=24) of non-insulin
therapies.
Self-reported changes of individual working practice showed 3 themes:
The ability to recognize and estimate carbohydrate(carb) in food is vital
in diabetes mellitus (DM), particularly for prandial insulin users, to ensure
matching of insulin dose to carbohydrate intake. Tools developed in the west
to gauge one’s carb counting ability have limited utility in Asian subjects, since
the Asian diet is different from a Western one with more varied/different carb
choices.
We aimed to develop and validate a carb and insulin dosing knowledge
quiz for Asian patients with DM. Items for the carb section were chosen from
commonly eaten food in Singapore based on food records from patients from
a diabetes centre in a single tertiary hospital. We tested: carb recognition in
food, single food carb estimation, meal carb estimation, food label reading;
insulin dosing for carb, blood glucose and for a meal. We compared the quiz
against dietitians’ and physicians’ rating of the patient’s carb and insulin
dosing knowledge respectively.
55 patients with DM on prandial insulin were recruited, with mean age of
42.6В±1.8 years, and insulin use duration of 8.4В±1.2 years. 54.5% were Chinese,
18.2% Malay and 27.3% Indian in ethnic origin. 60.4% of the subjects had type
1 DM, and 69.1% were on multiple daily dose of insulin(MDI) or insulin pump.
Mean score for the quiz was 64.7В± 2.3%. The total quiz score, carb domains
only and insulin dosing domains only were significantly correlated with the
respective healthcare provider ratings. Internal validity for the quiz was good,
with Cronbach alpha of 0.875 and Guttman split half coefficient of 0.923. Quiz
scores were significantly higher in type 1 DM subjects vs. type 2 (72.4В±2.3%
vs.54.5В±3.8%, p<0.001) and subjects with more complex insulin regimens
(MDI/CSII vs. bid: 70.0В±2.6% vs. 53.2В±3.4%, p<0.001).
Our preliminary analysis suggests that this quiz may be a useful screening
tool to assess carb and insulin dosing knowledge in Asian patients with
diabetes.
•Increased confidence and improved knowledge
•Improved assessment in choosing the correct therapy
•Improved advice to patients on lifestyle and medication
93.7%, n=164 of 175 responders would recommend the course.
Conclusion: This module enabled the delivery of a standardised training
to staff and increased confidence in managing (68%); administering (60%),
and prescribing (40%) non-insulin therapies. There is evidence to suggest that
the module led to changes in individuals working practice. Poor response rate
limits generalisability; but provides some indication of the early impact of this
intervention.
Nutrition—Clinical
25-LB
HbA1c Reduction With a Low Carbohydrate Diet and Skills that
Promote Behavior Change in Type 2 Diabetes Mellitus
LAURA SASLOW, SARAH KIM, JENNIFER J. DAUBENMIER, JUDITH T.
MOSKOWITZ, STEPHEN D. PHINNEY, VERONICA GOLDMAN, RACHEL M. COX,
PATRICIA MORAN, ELIZABETH MURPHY, FREDERICK M. HECHT, San Francisco,
CA, Davis, CA
We tested if a low carbohydrate (CHO) diet would improve glucose control
in overweight adults with type 2 diabetes or prediabetes. We randomized
participants with a HbA1c > 6.0% to a low fat, calorie restricted diet (LFCR;
restriction of 500 calories below estimated need for weight maintenance, 4550% of energy from CHO, 25-35% of energy from fat; n = 18) or a diet low in
CHO (LC; < 50 gm CHO/day not including fiber; n = 16). Both groups met for
13 sessions over 3 months. We excluded participants receiving insulin; 74%
were taking oral diabetes medications. All were also taught psychological
skills aimed at helping promote behavior change and maintenance. The
primary outcome was HbA1c. During the intervention period, the mean HbA1c
decreased -0.02% in the LFCR diet group and -0.59% in the LC group (p = 0.04
comparing groups). None in the LFCR group achieved an HbA1c < 5.7 compared
to 13% (n=2) in the LC group. Eleven percent of participants in the LFCR group
reduced or discontinued 1 or more oral diabetes medications whereas 47% in
the LC group did so. Mean weight loss was twice as high in the LC group, even
though they did not aim to calorie restrict but the LFCR group did. Despite its
relatively high fat content, blood lipids did not worsen on the LC diet. As this
was a small pilot with a short follow-up, further testing is warranted. However,
our results suggest that a lower carbohydrate diet coupled with skills that
promote behavior change may improve glucose control in type 2 diabetes.
Supported by: Alexandra Health
For author disclosure information, see page LB66.
ADA-Funded Research
LB7
Behavioral Medicine, Clinical Nutrition, Education, and Exercise
27-LB
In addition to previously reported robust face and content validity, these
psychometric analyses demonstrate the HypoA-Q has satisfactory structure,
internal consistency reliability, and validity (convergent, divergent, and known
groups). The HypoA-Q is likely to enable improved recognition of IAH and
evaluation of medical fitness for activities including driving. Its responsiveness
now needs to be examined in clinical trials.
Type 2 Diabetes: Effectiveness of Weight Loss Interventions on A1C,
Lipids, Blood Pressure
MARION J. FRANZ, JACKIE L. BOUCHER, Minneapolis, MN
A systematic review of weight loss interventions (WLI) in overweight/
obese adults with type 2 diabetes was conducted to determine their baseline
to 1-yr effectiveness. Study inclusion criteria: randomized clinical trial ≥1-year,
completion rate of ≥70%, published between Jan 2000 to Feb 2013. Ten studies
met study criteria; 7 compared WLI and 3 compared WLI to usual care/control. WLI
in 17 arms: meal replacements (2), individualized food plans (2), group behavioral
(2), low-fat (3), high monounsaturated fat (MUFA) (1), high carbohydrate (CHO)
(2), low CHO (2), high protein (1), Mediterranean-style diet (MED) (1), intensive
lifestyle intervention (ILI) (1). Weight losses: 14 WLI reported losses of 2.4 to
4.8 kg; the largest: MED, 6.2 kg and ILI, 8.4 kg; the smallest: low-CHO, 1.9 kg.
Figure 1 illustrates average weight losses per subject from WLI. Six WLI improved
1-yr A1C; however, 11 WLI reported NS A1C changes. Four trials compared WLI
with differing macronutrient percentages; weight changes did not differ between
groups (1.9 to 4.0 kg) and all reported NS changes in A1C. NS changes in lipids
were reported from the majority of the 17 WLI; 9 of 17 WLI reported ↑ in HDL-C, 3
of 17 ↓ in TG, 1 of 14 ↓TC, and 1 of 16 ↓ LDL-C. Five WLI reported positive blood
pressure changes and 3 NS changes. The ILI and the MED consistently reported
improvements in A1C, lipids, and blood pressure. All other WLI interventions
reported minimal, if any, benefits on these outcomes.
Supported by: Diabetes UK
29-LB
Evaluating the Effect of a Stage Matched Intervention or a Framing
Effects Intervention on LDL in Patients With Diabetes: Primary Results
of the TACTICS Trial
MARIA ANTONIA RODRIGUEZ, JENNIFER FRIEDBERG, SANGMIN JUNG, IRIS LIN,
JOHN CHOI, BINHUAN WANG, YIXIN FANG, JUDITH WYLIE-ROSETT, SUNDAR
NATARAJAN, New York, NY, Bronx, NY
Low-density lipoprotein cholesterol (LDL) is an established modifiable risk
factor for cardiovascular disease in diabetes and most patients are prescribed
treatment. Despite treatment, a substantial proportion have uncontrolled
LDL (LDL ≥ 100 mg/dL), probably because of patient nonadherence. Tailored
interventions hold promise to improve adherence. We evaluated if a stagematched intervention (SMI) based on the Transtheoretical Model or a framing
effects intervention (FEI) based on Prospect Theory will improve adherence
and lower LDL.
Veterans with diabetes and uncontrolled LDL were randomized to SMI, FEI,
or Attention Placebo (AP). LDL was assessed at baseline and 6 months. All
patients received monthly phone counseling for 6 months. SMI and FEI were
tailored to diet, exercise and medications. We evaluated the effect on LDL,
both as a continuous and as a dichotomous outcome, by initial unadjusted
analyses and then while controlling for baseline LDL and BMI in regression
models that accounted for physician clustering.
We randomized 247 veterans with Type 2 diabetes and hyperlipidemia. The
findings are summarized below.
The TACTICS (Targeting Adherence to Cholesterol-lowering
Treatment to Improve Control Study) Randomized Clinical Trial:
Primary Results
Framing Effects Intervention (FEI) Stage Matched Attention
p-value (statistical test or model)
Intervention (SMI) Placebo (AP)
Baseline (n=247; FEI 84, SMI 82, AP 81) comparisons of a) median LDL level (mg/dL) and b) LDL control %
(LDL < 100 mg/dL)
a) 105 mg/dL
112 mg/dL
111 mg/dL 0.12(Wilcoxon)
b) 42.17 %
28.75%
25.00%
0.05 (Chi-Sq test)
The effect on LDL at 6 months (n=222; FEI 75, SMI 73, AP 74) evaluated using: a) median LDL level (mg/dL), b)
LDL control % (LDL < 100 mg/dL), c) Linear regression and d) Logistic regression
a) 92 mg/dL
103 mg/dL
106 mg/dL FEI vs. AP= 0.005; SMI vs. AP = 0.46
(Wilcoxon)
b) 62.67%
46.58%
40.54%
FEI vs. AP = 0.01; SMI vs. AP = 0.46
(Chi-Sq test)
c) -10.80 mg/dL (95% CI: -20.5 - -1.1) -4.35 mg/dL (95% CI: Referent (0) FEI vs. AP= 0.03; SMI vs. AP = 0.42
-15.0 - 6.3)
(Linear model adjusted by baseline data)
Psychosocial, Behavioral Medicine
28-LB
Psychometric Validation of a Novel Measure of Impaired Awareness of
Hypoglycemia: The Hypoglycemia Awareness Questionnaire (HypoA-Q)
JANE SPEIGHT, SHALLEEN BARENDSE, BERIT INKSTER, BRIAN M. FRIER, JAMES
SHAW, Melbourne, Australia, Hornchurch, United Kingdom, Edinburgh, United
Kingdom, Newcastle upon Tyne, United Kingdom
Impaired awareness of hypoglycemia (IAH) affects 20-25% of adults with
established type 1 diabetes and is associated with a six-fold increase in severe
hypoglycemia. Our aim was to conduct preliminary psychometric validation of the
18-item HypoA-Q.
Questionnaires (HypoA-Q, Gold score, Clarke measure, Problem Areas in
Diabetes (PAID)) were completed by 120 adults with type 1 diabetes with/without
clinically diagnosed IAH (mean age: 44.4В±15.8 years; duration of diabetes:
22В±13.4 years; HbA1c 8.2В±1.3%; 44% women) attending routine specialist clinic
appointments. HbA1c was collected from clinic records.
Principal components analysis revealed the HypoA-Q to include three brief
scales reflecting �impaired awareness’, �symptom frequency’, and �symptom level’
(3-5 items each; Cronbach’s alpha=0.79-0.89), plus individual items measuring
recall of mild/severe hypoglycemic events, nocturnal hypoglycemia/awareness
and healthcare resource use. Satisfactory convergent validity was demonstrated,
e.g. between �impaired awareness’ and other measures of IAH (Gold: rs=0.75;
Clarke: rs=0.76). �Impaired awareness’ discriminated significantly between
those on the clinical register of IAH (n=60) and those not on the register (n=60;
U=640.00, p<0.001), correctly classifying 72% of participants. Divergent validity
was supported, e.g. with low correlations between �impaired awareness’ and
HbA1c (rs=-0.05), age (rs=0.16), duration of diabetes (rs=0.22), and diabetesrelated distress (PAID; rs=0.25).
d) Odds Ratio: 3.8 (95% CI: 1.6 - 9.0) Odds Ratio: 2.1 (95% Referent (Odds FEI vs. AP= 0.003; SMI vs. AP = 0.06
CI: 1.0 - 4.5)
Ratio = 1)
(Logistic model adjusted by baseline data)
The FEI lowered LDL and improved LDL control. This FEI may be a potent
facilitator for reaching lipid lowering goals in patients with Type 2 diabetes
and hyperlipidemia.
For author disclosure information, see page LB66.
ADA-Funded Research
LB8
Behavioral Medicine, Clinical Nutrition, Education, and Exercise
30-LB
32-LB
Vitamin D Supplementation Decreases Severity of Pain Symptoms
among Women With Type 2 Diabetes and Comorbid Depression:
Results from the Sunshine Study
After Baby Fitness Challenge (ABfC): Impacting Postpartum Weight in
Poor Rural Postpartum Women
DEBORAH L. YOUNG-HYMAN, SANDRA MOBLEY, MARLO VERNON, Augusta,
GA
TODD DOYLE, SUE PENCKOFER, PATRICIA MUMBY, MARY BYRN, MARY ANN
EMANUELE, DIANE WALLIS, Maywood, IL, Chicago, IL
The purpose of the study was to improve postpartum weight loss in poor rural
women. The intervention was integrated into a Healthy Start nurse managed
program improving healthcare for women and infants in East Central Georgia.
The intervention consisted of bi-weekly nutrition classes/supervised exercise
@ the local YMCA. The intervention facilitator provided social/problem solving
support via phone, email, Facebook, attending nutrition/PA sessions. Assessed
@ baseline (B), 6 and 12m were height/weight, wellbeing (I only, SF-12), and
nurse/interventionist contact. 104 women (18-43yrs; X BMI = 35.3 SD= 7.8;
89% AA) enrolled from non-contiguous counties (62 Intervention, 42 Control).
48 women retained (I=19, C=29) @ 12m. T-tests within and between group
characteristics @ B, 6 &12m calculated. Predictors significantly correlated
with BMI tested in linear regression models. Although absolute mean BMI was
greater for I @ B, BMI did not differ significantly between groups @ B, 12m, or
BMI change 0-12. BMI significantly increased in C (p < .002) from B to 12m, but
was stable for I mothers. For C, more case manager contact was associated
with greater 12m BMI (p <.01). For I, higher 12m BMI was associated with
lower B physical wellbeing (p< .01) and lower 6m (p< .04) mental wellbeing.
Predicting BMI change 0-12m for I, interventionist support (p <.02), number
of Y sessions attended (p < .08) and positive change in mental well-being
0-6m (p <.01) explained 72% of variance in BMI change 0-12. Women enrolled
in a nurse management Healthy Start program were shown to stabilize
post-partum weight from 6-18m when provided with a community based
intervention specifically focused on facilitating better nutrition and increased
PA. Attendance at supervised exercise sessions and interventionist support
both independently contributed to weight stabilization. Retaining women in
this high risk population remains a challenge. However this intervention model
shows promise for impacting obesity in poor rural women.
Type 2 diabetes (T2DM) is associated with complications such as depression
and pain. Few studies have examined how co-morbid pain impacts depression
treatment in patients (Ps) with T2DM. No studies have examined Vitamin D2
(25-OH-D) supplementation on this association. We aimed to 1) determine
if pain was affected by Vitamin D2 supplementation for treatment of Major
Depressive Disorder (MDD) in T2DM & 2) if differences in baseline (BASE)
pain were associated with changes in pain symptom severity over time.
The Sunshine Study was a single-arm repeated measures trial designed to
test the efficacy of weekly Vitamin D2 supplementation (50,000 IUs) for 6
months on MDD in women with T2DM. The Diabetes Symptom Checklist
subscales of neuropathic pain and sensory pain were used to measure pain
symptom severity at BASE & 3- & 6-month follow-ups (3MFU & 6MFU). Ps
(N=46) had a mean age of 54.6 years (SD=10.5), HbA1c=6.8% (SD=0.82%),
and T2DM duration=7.8 years (SD=7.1). 61% of Ps reported neuropathic pain
and 74% sensory pain at BASE. Repeated measures ANOVA showed clinical
improvements in neuropathic pain (F[2, 135]=2.25, p=.11, BASE M=3.2, 3MFU
M=1.8, 6MFU M=2.1) and sensory pain (F[2, 135]=1.76, p=.18, BASE M=7.3,
3MFU M=5.0, 6MFU M=5.9). There was a significant change in neuropathic
pain (F[2, 134]=34.5, p<.001) and sensory pain (F[2, 134]=28.1, p<.001)
according to BASE pain severity. Ps with higher neuropathic pain at BASE
(M=5.2) showed significantly (p<.05) decreased pain severity at 3MFU (M=2.5)
compared to Ps with lower neuropathic pain. Ps with higher sensory pain at
BASE (M=10.6) showed significantly (p<.05) decreased pain severity at 6MFU
(M=6.5) compared to Ps with lower sensory pain. Ps with elevated neuropathic
and sensory pain at BASE showed improved changes in pain severity at 3MFU
& 6MFU following Vitamin D2 supplementation for MDD in T2DM. Vitamin D2
supplementation for the treatment of pain and MDD in T2DM is promising.
Supported by: DHHS/HRSA (H59MC12788)
Supported by: NIDDK/NIH
Social Media Use by Individuals With Diabetes
33-LB
31-LB
Glucose Metabolism Is Associated With Acute and Chronic Stress in
Depressed Patients
EMILY SHAFFER-HUDKINS, NICOLE JOHNSON, STEPHANIE MELTON, Tampa, FL
LI LI, RICHARD C. SHELTON, Birmingham, AL
Patients with diabetes are often looking online for information and support
related to their chronic health condition. An analysis of the 10 most popular
social media websites tailored to individuals living with a chronic disease
found the sites to have an average of 6,700 members and up to 100 new
posts daily (Weitzman et al., 2011). The current study focuses on social
media use of patients with diabetes, given the high level of self-management
required and correlations with mental health and social support needs. In
recent examinations of online networking by patients with Type 1 (T1) and
Type 2 (T2) diabetes, researchers found the most common topics to include
sharing personal clinical information, requesting disease-specific guidance,
and receiving emotional support (Armstrong, et al., 2011). The purpose of the
current study was to address gaps in the current literature base and assist
health professionals in better understanding social support needs of this
population. A 14-item survey developed by the researchers was administered
to members from 4 national online diabetes communities. Participants
included 154 patients with a diagnosis of T1, T2, or gestational diabetes or
caregivers (i.e., parent/spouse). Descriptive statistics and thematic analyses
were used to determine patterns of social media use, perceived outcomes,
and suggestions for improving diabetes online communities. The majority of
respondents (81%) were patients; 62% were 18-30 years of age. The 3 most
frequently cited reasons for using diabetes-related social media included
1) having one’s voice heard, 2) finding information related to coping, and 3)
finding supportive personal stories from others. 72% reported experiencing
an improvement in their mood immediately after reading or sharing about
diabetes online. Recommendations to inform future social media content for
the diabetes community included: interdisciplinary input from medical and
mental health professionals, research explained in simple terms, use of humor,
and local community connections.
Early life stress (ELS) is recognized as a risk factor not only for psychiatric
disorders such as depression, but also for metabolic diseases including
prediabetes. Prediabetes is a state of abnormal glucose homeostasis
characterized by the presence of impaired fasting glucose, impaired glucose
tolerance, or both. Individuals with prediabetes are at increased risk for type
2 diabetes and cardiovascular diseases. The estimated cost of ELS-related
illnesses including depression and prediabetes in the U.S is over $200 billion
a year. Although numerous studies indicate a reciprocal relationship between
depression and diabetes, little is known about the association between
chronic and acute stress with prediabetes in depressed patients. Our aim is to
elucidate the relationship between acute psychosocial stress, ELS, i.e. sexual
and physical abuse, and glucose homeostasis in depressed patients. A history
of ELS is assessed using the Childhood Trauma Questionnaire. Depressed
patients and matched controls are exposed to an acute psychosocial stress,
Trier Social Stress Test (TSST), to assess acute social stress paradigm. Subjects
provide blood samples for oral glucose tolerance tests (OGTT). Fasting glucose
levels are positively correlated with the severity of depression and the severity
of sexual and physical abuse in depressed patients. Compared to controls,
depressed patients show impaired glucose tolerance during OGTT. Depressed
patients with higher fasting glucose levels have stronger acute stress
response represented by higher anxiety, fatigue and irritation scores during
the TSST. Pro-inflammatory cytokines such as interleukin-6 and interleukin-8
are elevated by the TSST in depressed patients compared with controls. These
results suggest a key relationship between glucose homeostasis, ELS and
acute stress in depressed patients. Our findings emphasize the importance to
identify and intervene stresses in depressed patients to improve their health
outcomes and to reduce the cost.
Supported by: The Patterson Foundation
For author disclosure information, see page LB66.
ADA-Funded Research
LB9
Clinical Diabetes/Therapeutics
34-LB
36-LB
We Are in this Together: Partner Perspectives of Living With a Loved
One With Diabetes
13C-Glucose
Breath Test Is a Valid and Highly Reliable Method to
Assess Insulin Resistance in Non Diabetic Mexican Adults
STEPHANIE MELTON, NICOLE JOHNSON, Tampa, FL
AZUCENA MARTINEZ BASILA, JORGE MALDONADO HERNГЃNDEZ, MARDIA
GUADALUPE LГ“PEZ ALARCГ“N, MARГЌA GUADALUPE, MATUTE GONZГЃLEZ,
Mexico City, Mexico
Partners or spouses play a significant role in providing diabetes support
and care for loved ones with Type 1 Diabetes. The demands of diabetes
care placed on partners are not significantly addressed or acknowledged in
the medical community. The purpose of this qualitative study is to assess
partner perceptions of how diabetes affects their personal relationship and
the challenges they face in caring for their loved one, as well as to identify
unmet needs for intervention.
In-depth interviews were conducted with 19 partners of individuals with
Type 1 Diabetes. The sample represents a diverse group of couples in
relationships from one to twenty-six years. Interview transcripts and notes
were analyzed for themes using a grounded theory approach with qualitative
software.
The challenges partners face revolve around the daily demands of diabetes
care and the emotional weight from worrying about their loved one. They
experience chronic stress, fear and grief over the risk diabetes poses for their
loved one.
They report experiencing grief over the loss of time with their spouse due to
expected shortened lifespan, they fear diabetes complications, and they worry
over having to provide emergency care for their significant other. However,
only 26% report receiving any form of diabetes education, while most (90%)
have administered life-saving care for their loved one. The role of the partner
is mediated by the perceived effectiveness of diabetes management. When
deemed necessary spouses take on a more active role in diabetes care, even
so, they struggle to not “nag” or overstep their loved one’s independence.
This study highlights the emotional strain partners face in providing
diabetes support. Partners need more psycho-social support services, care
giving training and formal diabetes education. The outcomes of this research
support the notion that incorporating spouses into diabetes care plans can
have positive impact on diabetes management and quality of life for families
impacted by diabetes.
Insulin Resistance (IR) constitutes a central abnormality in the pathogenesis
of type 2 diabetes mellitus; many attempts are being made to diagnose IR in at
risk individuals. Recently, the 13C-glucose breath test (13C-GBT), a noninvasive
technique, has been used to assess glucose metabolism in obese and diabetic
subjects. The aim of this study was to determine the repeatability and validity
of the 13C-GBT as a surrogate measurement of IR in non diabetic individuals.
To assess repeatability, 86 healthy volunteers were recruited; on the
likelihood that they would represent a spectrum of insulin sensitivities study
subjects, had a wide range of body mass indexes. All participants underwent
standard oral glucose tolerance tests plus 1.5 mg/Kg of U-13C-glucose (13C-GBT);
breath and blood samples were collected at baseline and at 10, 20, 30, 60, 90,
120, 150, and 180 min following the glucose load. The same procedure was
repeated within one week. To determine validity, 25 healthy volunteers were
recruited; they underwent the 13C-GBT, as previously described; and a week
later a hyperinsulinemic clamp (40 mU/m2*min) was performed.
Reliability was determined using Bland & Altman coefficients of variation
(CV); 13C-GBT proved to be a highly reliable method (CV 7.16%), and it has a
better reliability than other IR surrogates (HOMA 26.3%, fasting insulin 24.3%,
Matsuda DeFronzo Index 24.9%, 2h OGTT insulin 43.9%). To validate the test,
we computed correlation coefficients between the 13C-GBT and M and M/I
values derived from the clamp (0.65 and 0.66, P<0.0001). Using M/I value as
IR gold standard, a cutoff point of 4.435% for the 13C-GBT (expressed as % of
oxidized dose at 180min) showed a sensitivity of 79% and a specificity of 83%
(ROC curve AUC; 0.912, CI95 0.797-1, P=0.003).
Our results demonstrate that the 13C-GBT is reliable and valid, and may
represent a non invasive alternative to determine IR in non diabetic individuals
within a wide spectrum of insulin sensitivities.
Supported by: CONACYT
Supported by: The Patterson Foundation
37-LB
Clinical Trials of a Closed-Loop Artificial Pancreas With Large
Unannounced Meals
Clinical Therapeutics/New Technology—
Glucose Monitoring and Sensing
FRASER CAMERON, GГњNTER NIEMEYER, DARRELL M. WILSON, KARI BENASI,
PAULA CLINTON, B. WAYNE BEQUETTE, BRUCE A. BUCKINGHAM, Troy, NY,
Glendale, CA, Stanford, CT, Stanford, CA
35-LB
Closed-loop control of blood glucose (BG) levels in people with type 1
diabetes can reduce patient burden and the incidence of complications,
particularly if meals do not need to be announced. We tested a multiple
model probabilistic predictive controller (MMPPC) on four preliminary patients,
revised it and tested six primary patients. Each admission lasted for 32 hours
with five unannounced meals containing 1 g/kg of carbohydrate (CHO).
The closed-loop therapy used an Abbott Navigator CGM and Insulet insulin
pump with the MMPPC implemented through the UCSB artificial pancreas
system. Therapy began at 9 AM with unannounced meals at 9 AM, 1 PM, 5:30
PM, and 9 AM and 1 PM the next day. The patients had a mean (В±SD) HbA1C
of 7.3В±0.6%, age of 28В±5 years, total daily dose of 43В±13 U, and weight of
74±13 kg. The controller was initialized only with the patient’s total daily dose
and daily basal pattern.
The MMPPC algorithm explicitly estimates and predicts BG uncertainty
stemming from past and potential future meals, endogenous glucose
production, and insulin sensitivity. Insulin boluses are calculated to lower
predicted BG levels until there is a roughly 3% risk of BG levels below 80
mg/dl. At night, the MMPPC targets a BG level of 100 mg/dl with attenuated
control providing smooth corrections.
On a 24-hour basis, the primary patients had mean reference/CGM values
of 161/142 mg/dl, with 63/78% of time spent between 70 and 180 mg/dl.
Two preventable system failures led to a manual bolus (per subject settings)
and an underestimation of active insulin which subsequently required CHO
intervention for hypoglycemia. One other CHO treatment was given for a
nocturnal glucose of 66 mg/dl with a rate of change of -0.25 mg/dl per min.
For the 30 unannounced meals the mean pre-meal, post-meal maximum,
and 3-hour post-meal values were 139/132, 223/208, and 168/156 mg/dl
respectively.
The MMPPC was tested in-clinic against repeated, large, unannounced
meals and maintained good control overnight and during meals.
Improved Glycemia Early After Bariatric Surgery Is Largely Explained
by Caloric Restriction
SHELLEY YIP, MATTHEW SIGNAL, GREG SMITH, GRANT BEBAN, MICHAEL
BOOTH, RICHARD BABOR, TIM CUNDY, GEOFFERY CHASE, RINKI MURPHY,
Auckland, New Zealand, Christchurch, New Zealand
We assessed the acute impact of laparoscopic Roux-en-Y gastric bypass
(GBP) or sleeve gastrectomy (SG) or matched diet alone, on glucose excursion
in obese patients with type 2 diabetes and examined if this was mediated
by changes in insulin resistance, early insulin response (EIR) or gut hormone
levels. Six-day subcutaneous continuous glucose monitoring (CGM) recordings
were obtained from patients beginning 3 days before GBP (n=11), SG (n=10)
or matched diet (n=10) and analysed for glycemic changes. Glucagon like
peptide -1 (GLP-1), insulin, and glucose was measured during 75g oral
glucose tolerance testing at the start and end of each CGM. Post-operative
hyperglycemia occurred after both GBP and SG in the first 6 hours, with a
more rapid decline in glycemia after GBP (p<0.001). Beyond 24 hours postoperatively, glycemic variability as assessed by continuous overlapping net
glycemia action (CONGA), reduced after GBP (median [interquartile range] 1.6
[1.2-2.4] to 1.0 [0.7-1.3] p<0.05 and after SG 1.4 [0.9-1.8] to 0.7 [0.7-1.0] p<0.05),
similar to those on matched diet (2.2 [1.7-2.5] to 1.3 [0.8-2.8] p<0.05. Higher
logGLP-1 increment post oral glucose, occurred after GBP (mean В± SE, 0.80 В±
0.12 vs. 0.37 В± 0.09, p<0.05), but not after SG (0.43 В± 0.14 vs. 0.38 В± 0.11), or
after matched diet (0.18 В± 0.09 vs. 0.15 В± 0.07). Log EIR or insulin resistance
estimated by HOMA-IR did not change 3 days after any of the interventions
although oral glucose lowering therapies were stopped. In the subgroup with
>30% of baseline glucose >7mmol/L, mean glycemia and glycemic variability
improved 24 hours after both surgeries to a greater extent than matched diet.
Significantly higher GLP-1 increment and lower HOMA-IR was seen after GBP
in this subgroup. The acute impact of GBP and SG on improving glycemia
after the initial 24 hour period of post-operative hyperglycemia, is similar to
equivalent caloric restriction, despite higher GLP-1 increment after GBP.
Supported by: JDRF
Supported by: Jens Jensen Diabetes Fellowship; Auckland District Health Board
Charitable
For author disclosure information, see page LB66.
ADA-Funded Research
LB10
Clinical Diabetes/Therapeutics
Continuous Glucose Monitoring via Telemetry in Rat
38-LB
40-LB
A Study of Islet Auto-Antibodies and О’-Cell Functional of KetosisProne Diabetes
TAMER COSKUN, LIBBEY O’FARRELL, ROBERT BROCKWAY, PAUL HAEFNER,
RICHARD G. PETERSON, CHARLES V. JACKSON, Indianapolis, IN, St. Paul, MN
BAO MING-JING, Chengdu, China
The current standard for routine glucose measurements in preclinical
research is often glucometers and test strips. These pose significant limitations
in terms of accuracy, animal stress, and frequency of sampling. Until now,
continuous monitoring options for preclinical research have been very limited.
The present study evaluates the use of a novel prototype device (Data Sciences
International) for acute and chronic glucose measurements in rats. The device
is 1.4cc and provides temperature, activity, and direct continuous blood glucose
readings for 4 weeks or longer. The devices were evaluated in 4 diabetic and
4 normal Zucker fa/fa (ZDF) rats and in 10 Zucker diabetic/Sprague Dawley
(ZDSD) rats. Each animal was surgically instrumented with glucose sensors in
the abdominal aorta and the telemetry device placed in the intraperitoneal (ip)
cavity. Continuous glucose readings were recorded for 5-7 weeks with periodic
fasting GTTs (glucose, 2-3 g/kg, po or ip). Daily and GTT reference values were
recorded with a StatStrip Xpress glucometer (Nova Biomedical). The glucose
sensors provided high resolution data and demonstrated the ability to accurately
assess chronic diurnal patterns matching with the feeding pattern of rats from
3 days up to 7 weeks after surgery. These devices hold great potential for
comparing physiologic processes associated with glucose regulation in normal
and disease condition rats; monitoring diabetes progression and developing
preventive treatments for type II diabetes.
To observe the clinical characteristics, islet auto-antibodies, ОІ-cell function
in Ketosis-prone diabetes (KPD), and to investigate the effect of insulin
intensive therapy or oral antidiabetic drug (OHA) on the ОІ-cell in the patients
with KPD.
According to auto-antibodies (A) and ОІ-cell function (ОІ), a total of 162
patients with KPD were divided into four groups, including A+ОІ+ (group 1,
n=25), A-ОІ- (group 2, n=38), A+ОІ- (group 3, n=41), A-ОІ+ (group 4, n=58). Islet
auto-antibodies, including glutamic acid decarboxylase antibody (GAD-Ab),
insulin cell antibody (ICA), insulin autoantibody (IAA) and protein tyrosine
phosphatase antibody (IA-2Ab) were measured. The clinical characteristics,
biochemical parameters and FPG, 2h PG, HbA1c, FCP and 2h CP were compared
between each groups. Group 1, 2, 3 treated with insulin intensive therapy and
group 4 treated with Metformin (Glucophage). The treatment targets were FPG
<6.0mmol/L, 2hPG <8.0mmol/L, HbA1c<7%. After 6 months, Total 131 patients,
in each group were 21, 29, 34 and 47 cases finished this clinical test. At the
same time, ОІ-cell function and auto-antibodies were detected and analyzed.
Patients in group 2 demonstrated the youngest age at onset, lowest level of
FCP and 2hCP. Compared with group1, 2 and 3, patients in group 4 owned older
age at onset, higher BMI, more obese, dyslipidemia and hypertension, higher
FCP and 2h CP. The phenotype of patients in group 1 and 3 were intermediate
between group 2 and 4. After 6 months observation the ОІ-cell function showed
that the 2h CP of group 1 and 3 improved compared with basic value. In group
2, the 2h CP progressively deteriorated. So in group 4, FCP and 2h CP had no
changed.
There are significantly different in ОІ-cell function, auto-antibodies, clinical
characteristics and biochemical parameters in KPD who may need different
therapeutic strategies. Insulin intensive therapy may protect the ОІ-cell in
patients with KPD.
41-LB
Glucose Fluctuations in Patients During Acute Coronary Syndrome
Attack Might Be Associated With Cardiovascular Adverse Events and
the Change of CRP Level
XIAOLONG ZHAO, XIANGFEI WANG, YINMING LI, JUNBO GE, Shanghai, China
This study aimed to describe the glucose fluctuations pattern of patients
during acute coronary syndrome (ACS) attack using continuous glucose
monitor system (CGMS), and further observe the association between blood
glucose fluctuations and cardiovascular adverse events and prognosis related
biological markers. Patients suffered ACS confirmed with chest pain and
coronary angiography in cardiovascular intensive care unit were enrolled from
October 2011 to April 2012. A 72h retrospective CGMS was performed within
24 hours after admission. The main outcome is cardiovascular adverse events
during admission, the secondary outcome is prognosis related biological
markers such as C Reactive protein (CRP). A total of 38 patients (8 females,
30 males) were enrolled with age 64 В± 12 years old. Time of blood glucose
level higher than 10.0 mM or lower than 3.9 mM within 24 hours was 11.1h
(47.05%) and 0.267h (1.23%) respectively. The mean amplitude of glycemic
excursions (MAGE) was 6.49 В±2.48 mM. Patients were grouped by tertiles
according to MAGE distribution.There was no significant difference for clinical
parameters between three groups at baseline. But a significant change of CRP
(the difference between its level on 72h after admission and at admission)
during the stay in cardiovascular intensive care unit was observed. With the
increase in MAGE, the change in CRP level has an significant increase trend
in three group. The incidence rate of adverse cardiovascular events were
0/13, 1/13, 3/12 respectively that showed an non-significant increasing trend.
Patients suffered ACS appear to have an unsatisfactory glycemic control and
blood glucose fluctuations. The blood glucose fluctuation might be related to
the change of inflammatory markers CRP and adverse cardiovascular events.
39-LB
Comparison of Continuous Glucose Monitoring Systems in Type 1 Rat
Model
PAUL HAEFNER, KIMBERLY HOLLIDAY-WHITE, MARK CLEMENTS, St. Paul, MN,
Kansas City, MO
Presently, few continuous monitoring glucose options are available for
preclinical research. This study compares the performance of an existing
interstitial system (Medtronic MiniMed) with a fully implantable direct blood
monitoring prototype (Data Sciences International). Prototype sensors were
surgically implanted in the abdominal aorta of 10 weight matched Sprague
Dawley rats at 8 weeks of age. One week later, interstitial sensors were placed
in the dorsal skin near the scapulae and the rats dosed with streptozotocin
(65 mg/kg). Daily glucose measurements and approximately weekly GTT’s
(dextrose, 1-2.6 g/kg, ip; insulin, 0.5-1.0 unit/kg, im) were measured with
a StatStrip glucometer (Nova Biomedical). Sensors were calibrated via an
interpolated one point calibration method utilizing daily readings. A relative
absolute difference was calculated for each sensor, on both GTT’s and daily
readings. Diabetes was induced in 8 of 10 animals. Two of 10 interstitial
sensors and 2 of 10 blood monitoring sensors (improperly implanted) failed to
perform correctly. Both sensor types exhibited larger errors at lower glucose.
Interstitial sensors functioned an average of 5.6 days with an average delay of
8.8 minutes. Blood monitoring sensors functioned an average of 24.9 days with
an average delay of -0.8 minutes. These prototype devices provide a promising
alternative for chronic preclinical continuous glucose monitoring in a free
roaming type 1 rat model.
42-LB
Glucose Variability and Physical Activity Among People With Type 1
Diabetes
HANJONG PARK, LAURIE QUINN, ALI CINAR, CHANG PARK, KAMURAN
TURKSOY, ELIF SEYMA BAYRAK, ELIZABETH LITTLEJOHN, SARAH SCHWARZ,
DEIRDRE FISHER, Chicago, IL
Glucose variability (GV) and physical inactivity appear to contribute to the
development of diabetes complications in T1DM. A cross-sectional pilot study
was performed to examine relationships among demographics, GV, and physical
activity (PA) in 15 adults (10F/5M) using insulin pump therapy (ages:31В±13.3
years, duration of diabetes:20В±13.0 years; A1C:7В±0.8%; BMI:25В±5.0 kg/m2)
For author disclosure information, see page LB66.
ADA-Funded Research
LB11
Clinical Diabetes/Therapeutics
(meanВ±SD). PA measures for 48 hours were calculated using an accelerometer.
CGMS data for 48 hours were used to calculate GV measures (e.g., mean and
SD, %CV, mean of daily differences (MODD), continuous overall net glycemic
action (CONGAn), duration and area under curve (AUC) of hypo-, hyper-, and
euglycemia). Higher BMI was positively associated with higher CONGA1
and CONGA2 (rs = .557, p = .031; rs = .546, p = .035, respectively). People
with higher %CV (intra-day glucose variability) and higher MODD (inter-day
glucose variability) had longer duration and larger AUC of hypoglycemia (rs =
.623-.887, p values < .05). Higher %CV was associated with shorter duration
of hyperglycemia (rs = -. 650, p = .009). Duration of euglycemia negatively
related to the mean glucose value (rs = -.564, p = .028) and CONGA over a
3-hour interval (rs = -.529, p = .043). Duration and AUC of hyperglycemia were
negatively associated with step counts (rs = -.546, p = .035) and moderate and
vigorous PA (rs = -.518, p = .040). Longer duration and larger AUC of euglycemia
were consistently associated with more step counts (rs =.707, p =.003; rs =
643, p =.010, respectively) and longer light, moderate, and vigorous PA (rs=
.671, p = .006; rs = .671, p = .006, respectively). Less sedentary time tended
to lengthen duration of euglycemia (rs = -.604, p = .017) which competed with
duration of hyperglycemia. People with higher GV may have increased risk of
being overweight/obese and experience longer duration of hypoglycemia. PA
may be directly effective in reducing the duration and AUC of hyperglycemia,
decreasing the risk of developing diabetes complications.
[measured with a 100 mm visual analog scale (VAS)] of BIOD-238 and BIOD250 were compared to HU in 12 subjects with type 1 diabetes. Mean times
to half maximal insulin concentrations were 13.7 В± 1.9, 14.6 В± 1.9, and 24.8 В±
2.9 min for BIOD-238, BIOD-250, and HU, respectively (p<0.001 for BIOD-238
and p=0.001 for BIOD-250 vs. HU). Time to maximal insulin concentrations and
areas under the curves for the first 30 and 45 minutes for BIOD-238 and BIOD250 all indicated significantly increased early lispro absorption compared to
HU. The times to half maximal concentration after the peak were 123.8 В± 10.5,
132.3 В± 18.7 and 166.5 В± 10.6 min for BIOD-238, BIOD-250 and HU, respectively
(p=0.009 for BIOD-238 and p=0.016 for BIOD-250 vs. HU). The mean VAS score
was numerically lower, but not significantly different for BIOD-250 compared
to HU (2.7 В± 1.6 mm for BIOD-250 and 8.2 В± 4.5 mm for HU). The mean VAS
score for BIOD-238 was significantly higher than that associated with HU
(24.2 В± 7.0 mm, p=0.029 vs. HU). Safety results were comparable between
treatments. In conclusion, this study demonstrates that Na2EDTA/citrate
formulations of insulin lispro result in more rapid absorption and more rapid
declines from peak concentrations compared to HU. Furthermore, the presence
of magnesium sulfate in BIOD-250 significantly mitigates local injection site
discomfort without altering the ultra-rapid pharmacokinetic profile.
45-LB
Effect of Liraglutide Combined With Short-Term Continuous Insulin
Infusion on ОІ Cell Function in Newly Diagnosed Type 2 Diabetic
Patients
Supported by: NIH/NIDDK (R01DK085611-01), (P60DK020595-32S3)
WEIJIAN KE, JUAN LIU, LIEHUA LIU, HAI LI, DONGHONG FANG, YANBING LI,
Guangzhou, China
Clinical Therapeutics/New Technology—
Insulins
To investigate the effect on of Liraglutide combined with short-term
continuous insulin infusion (CSII) on ОІ cell function, newly diagnosed and drug
naГЇve type 2 diabetic patients with fasting plasma glucose of 7.0-16.7 mmol/L
were enrolled and randomly assigned to therapy with CSII (Group 1, n=19 )
or Liraglutide at a dose of 0.6 mg injected subcutaneously per day combined
with CSII (Group 2, n=20). The treatment was stopped after normoglycaemia
maintained for 2 weeks. Intravenous glucose tolerance tests (IVGTTs) were
performed to investigate acute insulin response (AIR) and blood glucose,
HbA1c, insulin were measured before and after.
The patients of Group 2 (Meadian=1 day) reached target glycaemic control in
less time than of Group 1 ( Meadian=2 days)(p=0.044). The daily insulin doses
of patients were not significantly different between 2 groups during the 2
weeks of maintaining normoglyceamia (day2: 0.68В±0.18 units/kg vs. 0.69В±0.15
units/kg, p=0.642; day7: 0.55В±0.21 units/kg vs. 0.57В±0.19 units/kg, p=0.842;
day13: 0.40В±0.16 units/kg vs. 0.47В±0.19 units/kg, p=0.299 ). And the HbA1c
of all patients had a considerable change after the treatment, while the level
of Group 1 decreased 1.77%В±0.16% and of Group2 decreased 1.475%В±0.17%
(p=0.21). The AIR improved significantly compared to baseline, however, the
improvement of Group 2 [ΔAIR=295.56±57.82 (uU•min/ml)] was much greater
than Group 1 [ΔAIR=79.96±18.63 (uU•min/ml)]( p=0.0013). The combination of
Liraglutide and CSII may have better effect in improving ОІ cell function than
CSII only.
43-LB
New Insulin Glargine Formulation: Glucose Control and Hypoglycemia
in People With Type 2 Diabetes Using Basal and Mealtime Insulin
(EDITION I)
MATTHEW C. RIDDLE, GEREMIA B. BOLLI, MONIKA ZIEMEN, ISABEL MUEHLENBARTMER, FLORENCE BIZET, PHILIP D. HOME, Portland, OR, Perugia, Italy,
Frankfurt, Germany, Paris, France, Newcastle upon Tyne, United Kingdom
Insulin glargine 100 U/mL (Gla-100) is widely used in people with type 2
diabetes (T2DM). A new insulin glargine formulation, 300 U/mL (Gla-300), has a
longer and a flatter pharmacokinetic profile than Gla-100. The phase 3 EDITION
I study compared the efficacy and safety of Gla-300 vs. Gla-100 in people with
T2DM using basal plus mealtime insulin. In a multicenter, open-label study
807 people [mean age 60 (SD 8.6) yr, duration of T2DM 15.8 (7.5) yr, BMI 36.6
(6.4) kg/m2, A1C 8.15 (0.78) %, total insulin dose 1.2 (0.47) U/kg, basal insulin
dose 0.67 (0.25) U/kg] were randomized (1:1) to once daily evening, Gla-300
(n=404) or Gla-100 (n=403) while continuing mealtime insulin. The dose was
titrated to achieve fasting plasma glucose 80-100 mg/dL. Primary endpoint
was change in A1C from baseline to month 6, and first secondary endpoint
was percent of people with ≥1 severe or confirmed (≤70 mg/dL) nocturnal
hypoglycemic event from month 3 to month 6. Gla-300 was non-inferior to
Gla-100 for change in A1C [least squares mean change -0.83% (0.06) in both
groups; difference -0.00% (95% CI -0.11 to 0.11)]. Fewer people using Gla-300
had severe or confirmed nocturnal hypoglycemia during month 3-month 6 (first
secondary endpoint: 36.1% vs. 45.5%; RR 0.79 [CI 0.67 to 0.94]; p=0.0070).
Occurrence of any hypoglycaemic event (% of people with at least one event)
during study period was numerically lower in the Gla-300 group than in the
Gla-100 group. No between-treatment differences in adverse events were
seen. In conclusion, in people with T2DM, Gla-300 was as effective as Gla-100
in controlling glycemia and was associated with a 21% reduction in severe
or confirmed nocturnal hypoglycemia from month 3 to month 6. Gla-300 was
well tolerated.
46-LB
The AUTONOMY Study: Initiating and Adjusting Lispro Therapy in
Patients With Type 2 Diabetes Mellitus Not Adequately Controlled on
Basal Insulin Therapy and Oral Agents
STEVEN V. EDELMAN, JENNAL JOHNSON, RONG LIU, LEONARD C. GLASS, San
Diego, CA, Indianapolis, IN
Evidence on optimal methods of prandial insulin initiation and adjustment,
especially in the primary care setting, is limited. AUTONOMY evaluated 2
approaches to introduce lispro therapy in patients with T2DM ≥18 to ≤85 yo,
on basal insulin glargine (GLA), NPH, NPL, or detemir (≥20 U/day) plus oral
antihyperglycemic agents for ≥3 months, with a screening HbA1c >7.0% to
≤12.0%, and who required prandial therapy. The 2 studies (A and B) were
conducted under 1 protocol as a 15‑country, multicenter, randomized, openlabel, parallel trial in 1106 subjects. Subjects were randomized to 1 of 2 bolus
insulin treatment algorithms for 24 weeks following a 6-week GLA optimization
period (for those not already optimized on GLA). Both algorithms added lispro
by 1, 2, or 3 injections, as needed, and subjects self-adjusted their prandial
insulin with study diaries, either every 3 days (Q3D), based on a current ADA/
EASD guidelines, or by 1 unit of insulin every day (Q1D). At Week 24 in each
study, the 2 algorithms showed an equivalent clinically significant drop in
HbA1c and low rates of hypoglycemia. AUTONOMY is the first to demonstrate
that prandial insulin therapy in T2DM on GLA can be effectively and safely
initiated in the primary care setting and that self-titration of lispro may be
done by either of 2 simple algorithms without the complexity of carbohydrate
counting and correction factor, regardless of patient age.
Supported by: Sanofi
44-LB
Lispro Formulations BIOD-238 and BIOD-250 Associated With Faster
Absorption and Declines From Peak Concentrations Compared to
HumalogВ®
ALAN KRASNER, LORI CANNEY, PHILIP PICHOTTA, PATRICK SIMMS, JANAKAN
KRISHNARAJAH, JOEY KAYE, ERROL DE SOUZA, Danbury, CT, Perth, Australia
Formulations of human insulin containing citrate and sodium-EDTA (Na2EDTA)
have been shown to be more rapidly absorbed than the commercially available
formulation of insulin lispro (HumalogВ®, HU). BIOD-238 is a Na2EDTA/citrate
formulation of lispro. BIOD-250 is a similar lispro formulation with the addition
of magnesium sulfate, intended to mitigate Na2EDTA-mediated local injection
site discomfort. In this single-center, randomized, double-blind three-period
crossover study, the pharmacokinetics and local injection site toleration
For author disclosure information, see page LB66.
ADA-Funded Research
LB12
Clinical Diabetes/Therapeutics
Hypoglycemia events were defined as >20 consecutive min of SG values ≤65
mg/dL without subject intervention; NH events were defined as those starting
between 10:00PM and 8:00AM. Subjects with T1D, ages 16-70 who had ≥2
NH episodes in a 2-wk run-in period were randomized to SAP+TS (121) or to
SAP (126).
Baseline A1C values were similar and did not change significantly in either
group, meeting the safety outcome. There was a 38% reduction in mean AUC
of NH events and a 32% reduction in rate of NH events in SAP+TS vs. SAP,
meeting the efficacy outcome. Overall, day and night combined, there was a
31% reduction in mean AUC of hypoglycemia events and a 30% reduction in
rate of hypoglycemia events in SAP+TS vs. SAP (Table). The percentage of SG
values <70 mg/dL was significantly less in SAP+TS vs. SAP (p<0.001).
No reported DKA occurred during the study. Four severe hypoglycemia events
occurred (4 subjects), all in the SAP group. ASPIRE In-Home demonstrated that
using SAP therapy with the TS feature safely reduced nocturnal and overall
hypoglycemia, without change in A1C.
A1C and Hypoglycemia Outcomes
A1C (%)
Hypoglycemia Events and Mean Event AUC
Nocturnal
Overall
Baseline
End of Events per AUC per Events per AUC per
Study patientevent
patientevent
week (mg/dL Г—
week
(mg/dL Г—
min)
min)
SAP + TS* 7.26В±0.71
7.24В±0.67 1.5В±1.0 980В±1200 3.3В±2.0
798В±965
SAP
7.21В±0.77
7.14В±0.77 2.2В±1.3 1568В±1995 4.7В±2.7 1164В±1590
CI or P value 95% CI: [-0.05, 0.15] p < 0.001 p < 0.001 p < 0.001 p < 0.001
*TS setting of 70 mg/dL
47-LB
Glycemic Control and Treatment Satisfaction in Type 2 Diabetes: Basal
Plus Compared With Biphasic Insulin in the LANSCAPE Trial
JITEN VORA, NEALE COHEN, MARC EVANS, ANDREW HOCKEY, JANE SPEIGHT,
CAROLINE WHATELY-SMITH, Liverpool, United Kingdom, Melbourne, Australia,
Cardiff, United Kingdom, Guildford, United Kingdom, Hornchurch, United Kingdom,
Hunton Bridge, United Kingdom
Biphasic insulin is a frequent intensification step when basal insulin alone
provides inadequate glycemic control. Basal plus main-meal fast acting insulin
may be equally effective and more acceptable. The LANSCAPE study tested
whether “Basal Plus” insulin glargine (Lantus) once daily and insulin glulisine
(Apidra) at main meal was non-inferior to twice daily “Biphasic” insulin aspart/
aspart protamine 30/70 (NovoMix30) with respect to glycemic control (primary
objective) and provided superior treatment satisfaction.
LANSCAPE was an international, controlled trial of adults with type 2 diabetes
receiving basal insulin. Participants’ mean (SD) age was 61.6 (8.5) yrs, diabetes
duration 12.9 (6.4) yrs and A1C 8.62 (0.94) %. During an 8-12 week run-in, oral
agents except metformin were stopped and insulin glargine optimized. After run
in, 335 participants with fasting glucose at target (<126mg/dl) but suboptimal
A1C (>7%) were randomized to a “Basal Plus” (n=170) or “Biphasic” (n=165)
regimen. Active insulin titration followed standardized algorithms; 89% of
patients (91.8% and 86.1% respectively) completed treatment.
At 24 weeks A1C fell by 1.00% in the Basal Plus, 1.22% in the Biphasic
arms; mean difference 0.21% (SE 0.09, upper 97.5% CL 0.38), implying noninferiority of Basal Plus relative to the Biphasic regimen (pre-defined margin
0.4%). More subjects reached target A1C 7% with Basal Plus than Biphasic
(76.5% vs. 66.1%, p=0.049). There was no difference in overall hypoglycemia
rates (15 vs. 18 events/patient-year respectively p=0.2), but slightly more
nocturnal events with Basal Plus (5.7 vs. 3.6 events/patient-year p=0.02).
Significant advantages favoring Basal Plus were seen in DTSQc and ITSQ
treatment satisfaction measures.
In type 2 diabetes Basal Plus provides comparable glycemic control to a
Biphasic regimen, better patient reported outcomes, and may present a more
acceptable option for insulin initiation/intensification.
49-LB
Glucose Lowering Effects of Pre-Meal Pramlintide During ClosedLoop Insulin Delivery Is Associated With Lower Plasma Glucagon
Levels and Reduced Insulin Requirements
MILADYS PALAU-COLLAZO, JENNIFER L. SHERR, LORI R. CARRIA, EDA CENGIZ,
ANIRBAN ROY, WILLIAM V. TAMBORLANE, EILEEN M. TICHY, KATE WEYMAN,
STUART A. WEINZIMER, New Haven, CT, Northridge, CA
Exaggerated prandial glycemic excursions in type 1 diabetes (T1D) persist
during closed-loop control (CLC), due in great part to delays in the absorption
of subcutaneously infused insulin analogs. We previously demonstrated
that pre-meal 30 mcg pramlintide injections in T1D subjects mitigated but
did not normalize glycemic excursions during CLC. In this study, we sought
to determine whether the improved meal excursions during CLC could be
achieved with therapeutic 60 mcg pre-meal doses of pramlintide and the
mechanism underlying such improvements in post-meal hyperglycemia. Ten
subjects (4 males, age 16.9-23.2 y, A1c 7.2В±0.6%) underwent two 24-hour
CLC assessments: CL alone (Control) and then CLC plus pramlintide (Pram),
separated by 3 weeks, during which time pramlintide was introduced and
increased gradually to the full 60 mcg per meal dose. Identical meals were
provided for both study days, and there were no meal announcement strategies.
Pramlintide reduced overall mean prandial glycemic excursions during CLC from
93В±10 to 59В±20 mg/dL (p<0.001), a value that was significantly (p<0.020) lower
than previously observed with the 30 mcg pre-meal dose. Mealtime insulin
delivery also fell with pramlintide from 11.4В±3.2 units to 9.4В±2.9 units/meal
(p<0.005). As shown in the Figure, the peak peak-post-meal glucose during CLC
with and without pramlintide correlated with peak post-meal plasma glucagon
concentrations. These data indicate that the reduction in prandial glycemic
excursions during CLC by pramlintide is related to suppression of mealstimulated glucagon responses which, in turn, contributes to substantially
lower meal related insulin requirements.
Supported by: Sanofi
Clinical Therapeutics/New Technology—
Insulin Delivery Systems
48-LB
Supported by: NIDDK (R01DK085618); JDRF (22-2009-799); NIH (UL1RR024139)
Reduction in Hypoglycemia and No Increase in A1C With ThresholdBased Sensor-Augmented Pump (SAP) Insulin Suspension: ASPIRE
In-Home
50-LB
Successful Utilization of a Computer-Guided Glucose Management
System for a Surgical Care Improvement Project at a Tertiary Care
Hospital
RICHARD M. BERGENSTAL, DAVID C. KLONOFF, BRUCE W. BODE, SATISH K.
GARG, ANDREW AHMANN, ROBERT SLOVER, MELISSA MEREDITH, FRANCINE
R. KAUFMAN, ASPIRE IN-HOME STUDY GROUP, Minneapolis, MN, San Mateo,
CA, Atlanta, GA, Aurora, CO, Portland, OR, Madison, WI, Northridge, CA
ROBERT J. TANENBERG, SANDRA D. HARDEE, HERBERT G. GARRISON, GreenВ­
ville, NC
ASPIRE In-Home was a 3-month RCT comparing SAP with Threshold Suspend
(SAP+TS), which stops insulin at a specified sensor glucose (SG) threshold for
up to 2 h, to SAP alone (SAP).
The primary safety outcome was the between-group difference for О”A1C.
The primary efficacy outcome was the between-group difference for AUC
of nocturnal hypoglycemia (NH) events, measured by Enlite CGM sensors.
Background: Endotoolв„ў is a computer-guided glucose management system
for administration of intravenous insulin in hospital intensive care units. The
Surgical Care Improvement Project (SCIP) is a national quality based effort to
improve surgical outcomes in U.S. hospitals.
Methods: In 2008, the Endotool system was initiated in the surgical
and cardiothoracic intensive care units of Vidant Medical Center, an 850
For author disclosure information, see page LB66.
ADA-Funded Research
LB13
Clinical Diabetes/Therapeutics
52-LB
bed tertiary care hospital. The SCIP criteria for glycemic control were the
percentage of glucose values in the target range on post-op day two. We also
measured avoidance of hospital acquired (never pay) glycemic conditions such
as hypoglycemic coma or diabetic ketoacidosis. Data was provided by CMS,
the CDC and the National Health Care Survey.
Results: Immediate and sustained improvement in SCIP was noted starting
from 88% in 2008 to 99% in 2011, compared to the national average of 95%.
This data represents a doubling in cost savings and places our hospital in
the top 10% of all U.S. hospitals for SCIP. In addition, we noted immediate
and sustained reductions in hospital-acquired conditions improved from
0.083/1000 in 2008 to 0.032 in 2011 compared to the national average of
0.058/1000. Conclusions: The Endotoolв„ў intravenous insulin system used in
our hospital surgical ICUs resulted in a dramatic improvement in SCIP and a
reduction in hospital acquired (never pay) glycemic conditions with a highly
favorable economic impact.
HARMONY 3: 104 Week (Wk) Efficacy of Albiglutide (Albi) Compared
to Sitagliptin (Sita) and Glimepiride (SU) in Patients (pts) With Type 2
Diabetes Mellitus (T2DM) on Metformin (Met)
BO AHRÉN, MURRAY STEWART, DEBORAH CIRKEL, FRED YANG, CAROLINE
PERRY, SUSAN JOHNSON, Lund, Sweden, Upper Merion, PA, Stevenage, United
Kingdom, Research Triangle Park, NC
This 3-year, randomized, double-blind, placebo (Pbo)- and active-controlled,
Phase III study examined Albi 30 mg added to Met vs. Pbo + Met, Sita + Met,
or SU + Met in pts with T2DM (A1C 7-10%) on Met. Pts meeting predefined
hyperglycemia criteria qualified for blinded dose titration (SU 2 to 4 mg,
albiglutide 30 to 50 mg). Primary endpoint was the mean difference in A1C
change (∆) from baseline at Wk 104.
For A1C (baseline 8.1В±.8%), Albi treatment (txt) difference was superior to
Pbo (в€’.91%; P < .0001), Sita (в€’.35%; P = .0001) and SU (в€’.27%; P = .003). Albi
had superior txt difference (P < .05) in FPG (mg/dL) vs. comparators: Pbo в€’27.7;
Sita −15.5; SU −10.1. Weight (baseline 90.7 kg±19) (kg) ∆ was similar for Albi
(P = NS) compared to Pbo (txt difference: в€’.2) and to Sita (в€’.4). Weight loss was
greater with Albi than SU (txt difference: в€’2.4; P < .0001).
Gastrointestinal AEs through Wk 104 with Pbo/Sita/SU/Albi were: nausea,
11%/7%/6%/10%; diarrhea, 11%/9%/9%/13%; vomiting, 1%/4%/4%/6%.
Injection site reactions occurred in: Pbo 5%, Sita 6%, SU 8%, Albi 17%. The
incidence of documented (≤70 mg/dL) symptomatic hypoglycemia events (prior
to the addition of hyperglycemia rescue medication) was Pbo 4%, Sita 2%, SU
18%, Albi 3%; no severe events.
Albi treatment for T2DM as add on to met was durable and superior to Sita
and SU in A1C and FPG reduction, superior in weight loss to SU, and well
tolerated at Wk 104.
Clinical Therapeutics/New Technology—
Non-Insulin Injectables
51-LB
Antisense Suppression of Serum ApoC-III Improves HypertriВ­glyceriВ­
demia and Insulin Sensitivity in Multiple Species
RICHARD G. LEE, MARK J. GRAHAM, WUXIA FU, VERONICA J. ALEXANDER,
WALTER SINGLETON, RICHARD GEARY, JENNIFER BURKEY, SANJAY BHANOT,
ROSANNE M. CROOKE, Carlsbad, CA
Chronic elevation in fasting serum triglycerides (TG) is a hallmark of
metabolic syndrome and type 2 diabetes (T2D). A key regulatory factor in
TG homeostasis is apolipoprotein C-III (apoC-III), an apolipoprotein present
on VLDL, LDL and HDL particles. We have previously demonstrated in rodent
models, monkeys, and normal human volunteers that antisense oligonucleotide
(ASO) mediated suppression of apoC-III concomitantly reduced serum TG, with
no target-related safety issues observed. In BB rats, a model of human type 1
diabetes, apoC-III ASO treatment produced a significant delay in pancreatic
beta cell death, demonstrating that apoC-III may represent an important factor
in disease progression. In Western diet fed human apoC-III transgenic mice,
treatment with the human apoC-III ASO for eight weeks produced concordant
and significant reductions in hepatic human apoC-III mRNA (~87% reduction vs.
control ASO), plasma human apoC-III protein (79 В± 6 mg/dL with apoC-III ASO
vs. 173 В± 1 mg/dL with control ASO) and fed plasma TG (227 В± 16 mg/dL with
apoC-III ASO vs. 889 В± 59 mg/dL with control ASO). Fed plasma insulin levels
were also reduced (1.8 В± 0.1 ng/ml with apoC-III ASO vs. 5.8 В± 1 ng/ml with
control ASO) without a change in plasma glucose concentrations, indicating an
improvement in insulin sensitivity. A Phase 2 double-blind placebo controlled
study is underway in dyslipidemic T2D patients to determine whether apoC-III
ASO treatment will improve insulin sensitivity as assessed by hyperinsulinemiceuglycemic clamps conducted pre and post 3 month ASO administration, as
well as potential reductions in glucose, insulin and hemoglobin A1c levels.
Initial data suggest that therapeutic targeting of apoC-III may represent an
attractive strategy for reducing serum TG and improving insulin sensitivity in
T2D individuals.
Supported by: GlaxoSmithKline
53-LB
Superagonistic Activation of GLP-1 Receptor by CA Exendin-4
(Exendin-4 Analog) With Fast Dissociation Rate Constant
IN YOUNG CHOI, SUNG HEE PARK, SANG YOUN HWANG, KYU HANG LEE,
YOUNG HOON KIM, SE CHANG KWON, Hwaseong-si, Republic of Korea
Exendin-4 is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the
treatment of type 2 diabetes. We have developed a novel Exendin-4 analog,
CA Exendin-4, which showed potent insulinotropic and glucose lowering
activity by N-terminal modification. Surface Plasmon resonance (SPR) analysis
revealed CA Exendin-4 dissociated 5.5-fold faster than native Exendin-4 from
human GLP-1 receptor (GLP-1R). CA Exendin-4 showed greater in vitro cyclic
AMP accumulation and insulin release in a rat insulinoma cell line and was
more effective in glycemic control in db/db mice. We supposed that the
fast dissociation of CA Exendin-4 might elicit less internalization of GLP-1R
so that it enhanced GLP-1 signaling. In the receptor internalization assay,
significantly less internalization of GLP-1R was confirmed in the CA Exendin-4
treated cells. We have conjugated human Fc fragment to CA Exendin-4 and
Exendin-4, named langlenatide and HM11260A respectively, to give prolonged
half-life. Their binding properties to GLP-1R were conserved similarly with CA
Exendin-4 and Exendin-4 even after conjugation. The glucose lowering efficacy
of langlenatide was compared with that of HM11260A in db/db mice, and the
result showed much more potent efficacies were achieved in langlenatide
treated group. These results suggest that the rapid dissociation kinetics on
GLP-1 receptor triggers superagonistic activation and resulted in potent
efficacy outcome.
For author disclosure information, see page LB66.
ADA-Funded Research
LB14
Clinical Diabetes/Therapeutics
55-LB
HARMONY 2 Wk 52 Results: Albiglutide Monotherapy in Drug NaГЇve
Patients With Type 2 Diabetes Mellitus
MICHAEL NAUCK, MURRAY STEWART, CHRISTOPHER PERKINS, ANGELA
JONES-LEONE, FRED YANG, CAROLINE PERRY, RICKEY REINHARDT, MARC
RENDELL, Harz, Germany, Upper Merion, PA, Winston-Salem, NC, Omaha, NE
This 3-year, double-blind, placebo (PbO)-controlled study examined efficacy/
safety of GLP-1 receptor agonist albiglutide at 30mg (Albi30) and 50mg (Albi50)
vs. placebo (PbO) in patients with A1C (7в€’10%) on diet and exercise. Both
Albi groups began Albi30 QW (Albi50 started at Wk 12) and were allowed
to continue if requiring hyperglycemic rescue (R). Primary objective was A1C
change from baseline at Wk 521 with statistical testing performed for Albi50
vs. PbO then Albi30 vs. PbO.
Baseline characteristics were similar between groups; mean A1C 8.1%;
mean age 53 years; BMI 34 kg/m2; duration of diabetes 4 years. Wk 52 A1C
difference(Albi в€’ Pbo) was в€’0.84% (95% CI в€’1.11, в€’0.58) for Albi30 and в€’1.0
4% (95% CI в€’1.31, в€’0.77) for Albi50; both P<.0001. Fasting plasma glucose
decreased rapidly and the improvement mirrored A1C out to 52 wks:в€’34 mg/
dL (95% CI в€’46, в€’22) for Albi30 and в€’43 mg/dL (95% CI в€’55, в€’31) for Albi50,
both P<.0001. Weight (kg) decreased in all groups: PbO: в€’0.7, Albi30: в€’0.4,
Albi50: в€’0.9. GI adverse events (% participants including R) for Pbo/Albi30/
Albi50 were: nausea 8/10/9; diarrhea 12/10/13; vomiting 1/3/3. Injection site
reactions (% participants including R) were higher for Albi30 (18) and Albi50
(22) vs. Pbo (10). Incidence of pre-R documented (≤70 mg/dL) symptomatic
hypoglycemia events (%) was Albi30 (1) and Albi50 (0) vs. Pbo (2); no severe
events reported.
Albi monotherapy resulted in robust, durable A1C reduction through Wk 52
and was well tolerated.
Correlation of fast dissociation kinetics of CA Exendin-4 and insulinotropic activity. (A) The receptor affinity
of CA Exendin-4 was measured by a SPR assay using immobilized extracellular domain of human GLP1 receptor which is fused to the GST (glutathione S transferase). The hGLP-1R/GST was expressed in
the transformed CHO cell and purified by GST affinity chromatography. The sensorgram of CA Exendin-4
showed a rapid dissociation rate compared with Exedin-4. (B) Insulinotropic activity was measured by
murine RINm5F cells. The magnitude of maximal insulinotropic activity was 2-fold higher on CA Exendin-4
(P<0.05).
54-LB
HARMONY 4: 52-Wk Efficacy of Albiglutide (Albi) vs. Insulin Glargine
(Glar) in Patients (pts) With T2DM
RICHARD E. PRATLEY, MURRAY STEWART, DEBROAH CIRKEL, JUNE YE,
CAROLINE PERRY, MOLLY C. CARR, Orlando, FL, Upper Merion, PA, Stevenage,
United Kingdom, Research Triangle Park, NC
This 3-year, randomized, open-label, parallel-group, multicenter, Phase III
study assessed efficacy + safety of Albi, a once-weekly (QW) GLP-1 receptor
agonist, at 30 mg QW vs. Glar in T2DM pts uncontrolled (A1C 7-10%) on a
regimen of metformin (met) В± sulfonylurea (SU). Pts were treated to a target
A1C ≤7.0% and FPG ≤100 mg/dL. If needed, pts could uptitrate Albi to 50 mg
QW and Glar per prespecified criteria. The primary objective was to evaluate
the A1C change from baseline at wk 52 in Albi vs. Glar. Pts were allowed to
continue if hyperglycemic rescue was required.
Baseline demographics were similar between groups; mean age 56 y, BMI
33 kg/m2, A1C 8.3%, duration of diabetes 8.8 y, 82% receiving met + SU. A1C
decreased in both groups. The wk 52 treatment difference was 0.11% (95% CI
в€’0.04%, 0.27%). The upper bound of the CI was below the noninferior margin
of 0.3%, indicating noninferiority of Albi to Glar. Change in FPG significantly
favored Glar, whereas change in weight significantly favored Albi. AEs through
wk 52 for Albi/Glar were nausea 9.9%/3.7%; diarrhea 7.5%/4.1%; vomiting
3.8%/3.7%. Documented (≤70 mg/dL) symptomatic hypoglycemia and severe
hypoglycemic events (prior to the addition of hyperglycemia rescue meds)
were less with Albi vs. Glar (18%/0.4% vs. 27%/0.4%). Injection site reactions
occurred in 13.9% of Albi and 8.7% of Glar pts.Albi treatment resulted in A1C
improvement at wk 52 that was noninferior to Glar with modest weight loss.
Both drugs were well tolerated.
Supported by: GlaxoSmithKline
56-LB
Human Tissue Kallikrein (DM-199 Compound) Induces DiabetesProtective Immunomodulation in NOD Mouse T1D Model
ALEXEI Y. SAVINOV, LILIA MANEVA-RADICHEVA, CHRISTINA AMATYA, CAMILLE
PARKER, JACOB ELLEFSON, ILIAN RADICHEV, JACAN SIMON, PAUL BURN, MATT
CHARLES, MARK WILLIAMS, Sioux Falls, SD, Minneapolis, MN
Recombinant human tissue kallikrein-1 (DM-199) is currently under
development for the treatment of both Type 1 and Type 2 diabetes mellitus. We
previously reported significant dose- and frequency-of-treatment- dependent
effects including attenuation of spontaneous T1D development in female NOD
mice and herein the mechanistic studies are presented.
The T1D-protective DM-199 action depended on the reduced rates of islet
infiltrates formation, which lead to significantly improved preservation of ОІ
cell mass and function. Specifically after 18 weeks of treatment there was an
increased retention of naive CD8+ T cells in the spleen, and a commensurate
decrease in numbers of activated CD8+ cells in pancreatic lymph nodes (PLN)
(up to 27% reduction; p=0.002) and islet infiltrates (up to 2-fold reduction in
CD4/C8 T cell ratios; p=0.008). Treatment with DM-199 yielded a significant
increase of percentage of T regulatory cells (Tregs: CD4+, CD25+, Foxp3+) in
both the PLN (2.5%, p=0.014) and pancreata (~4%, p=0.0032) suggesting a
change in CTL trafficking and an increase in the Treg populations to reduce
insulitis.
The Tregs appeared to be induced by an increase in active TGFОІ (up to
63%, p<0.05) with no effect on total TGFОІ. An increase in the expression
of Indoleamine 2,3-dioxygenase in dendritic cells (30%, p<0.001) was also
Supported by: GlaxoSmithKline
For author disclosure information, see page LB66.
ADA-Funded Research
LB15
Clinical Diabetes/Therapeutics
observed which could explain the increase in the Treg populations in vivo. The
increase in Tregs is also of interest in the treatment of diabetic nephropathy
where Treg dysfunction appears to correlate with disease. In summary DM-199
could represent a novel medicament for the treatment of both Type 1 and 2
diabetes, to be elucidated in upcoming clinical trials.
site reaction reports with albiglutide vs. placebo and vs. pioglitazone, and
more hypoglycemic events with pioglitazone and albiglutide (Table).
Albiglutide in triple therapy gives effective glucose lowering and
was generally well tolerated and associated with less weight gain than
pioglitazone.
57-LB
HARMONY 1 Week 52 Results: Albiglutide vs. Placebo in Patients With
Type 2 Diabetes Mellitus Not Controlled On Pioglitazone В± Metformin
JANE REUSCH, MURRAY STEWART, CHRISTOPHER PERKINS, PAUL ORDRONNEAU,
JUNE YE, CAROLINE PERRY, RICKEY REINHARDT, BRUCE BODE, Denver, CO,
Upper Merion, PA, Winston-Salem, NC, Research Triangle Park, NC, Atlanta, GA
This 3-year, randomized, double-blind, placebo (Pbo)-controlled study
evaluated efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide
30mg (Albi) + Pio В± Met vs. Pbo + Pio В± Met in patients inadequately controlled
(A1C 7-10%) on Pio В± Met. Patients were allowed to continue if requiring
hyperglycemic rescue (R). Primary objective was A1C change from baseline
at week 52.
Baseline demographics were similar between groups; mean A1C 8.1%;
mean age 55 years; BMI 34 kg/m2, duration of diabetes 8 years. Week 52
change from baseline A1C was в€’0.05% for Pbo and в€’0.81% for Albi, treatment
difference (TD): в€’0.75% (95% CI в€’0.95%, в€’0.56%),
P < .0001. Fasting plasma glucose declined rapidly and the improvement
mirrored A1C out to 52 weeks (+6.4 mg/dL for Pbo, в€’23.1 mg/dL for Albi, TD:
в€’29.5 mg/dL, P < .0001. There was a nonsignificant difference in weight with
Albi vs. Pbo (+0.45 kg for Pbo, +0.28 kg for Albi, TD: в€’0.18 kg). Adverse events
(% participants including R) of nausea and vomiting were comparable between
Albi/Pbo (10.7%/11.3% and 4.0%/4.0%, respectively) while diarrhea was
higher with Albi (11.3% vs. 8.6%) and injection site reactions were higher for
Albi (11.3%) vs. Pbo (7.9%). Incidence of pre-R documented symptomatic (≤70
mg/dL) and severe hypoglycemia was 1%/0% Pbo vs. 3%/1% Albi.
Albi combination therapy resulted in a robust and sustained glycemic
improvement with good tolerability in patients with type 2 diabetes mellitus.
Supported by: GlaxoSmithKline
59-LB
HM11260C, a New Generation Long Acting GLP-1R Agonist With a
Unique Pharmacokinetic Profile Improves Glucose Control and GI
Tolerability: A Phase Iia Clinical Trial in Type 2 Diabetes Mellitus
JAHOON KANG, SOOMIN CHOI, IN YOUNG CHOI, SE CHANG KWON, MICHAEL
TRAUTMANN, MARCUS HOMPESCH, JEEWOONG SON, Seoul, Republic of Korea,
Hwaseong-si, Republic of Korea, Chula Vista, CA
A very long T1/2(~ 180 hrs) and no burst absorption (Tmax:: ~144 hrs) of
HM11260C was confirmed in previous single ascending dose study in T2DM.
The aim of this double-blinded, randomized, placebo controlled phase IIa study
is to investigate safety, tolerability, PK and PD of HM11260C when treated
repeatedly with weekly or monthly regimens in T2DM. HM11260C was
administered subcutaneously over an 8-week for weekly regimens or a 9-week
for monthly regimens.
Data through Day 57 from 48 patients in W1 (1 mg/wk), W2 (2 mg/wk), W3
(4 mg/wk), M1 (8 mg/mo) and M2 (12 mg/mo) are reported. Key demographics
were (active vs. placebo; mean [SD]): age, 53.3 [7.0] vs. 52.9 [8.7] years; HbA1c,
8.4 [1.0] vs. 8.1 [0.9] %. At Day 57, patients treated with weekly regimens
or monthly regimens experienced clinical significant improvements from
baseline HbA1c, fasting plasma glucose, body weight compared with placebo.
Most common AEs were nausea, vomiting and diarrhea. Weekly regimen
showed fewer GI AEs and most events were reported after first injection. No
treatment effect was observed on vital signs, laboratory and ECG. HM11260C
demonstrated meaningful improvements in blood glucose control and good
tolerability after repeated treatment in all weekly and monthly cohorts. Further
development of HM11260C is warranted to explore its full potential as mono
and combination therapy in patients with T2DM.
Supported by: GlaxoSmithKline
58-LB
52-Week Efficacy of Albiglutide vs. Placebo and vs. Pioglitazone in
Triple Therapy (Background Metformin and Glimepiride) in People
With Type 2 Diabetes: HARMONY 5 Study
PHILIP HOME, MURRAY STEWART, FRED YANG, CAROLINE PERRY, MOLLY C.
CARR, Newcastle upon Tyne, United Kingdom, Upper Merion, PA
A randomized, double-blind, multicenter study evaluated the efficacy and
safety of the GLP-1 receptor agonist albiglutide once weekly (QW) vs. placebo
and vs. pioglitazone all on background metformin and glimepiride in people
with A1C 7.0-10.0% on dual therapy. The primary objective was A1C change
from baseline at week 52. Uptitration of albiglutide 30 mg to 50 mg QW
and pioglitazone 30 mg to 45 mg QD was allowed if needed. Patients were
allowed to continue if hyperglycemic rescue was required. Stepwise statistical
analysis was first vs. placebo, then noninferiority (margin 0.30%) testing vs.
pioglitazone.
Baseline mean age was 55.2 years, BMI 32.2 kg/m2, A1C 8.2%, duration of
diabetes 8.9 years. Week 52 A1C difference (albiglutide - placebo) was в€’0.87
(95% CI в€’1.07, в€’0.68) % (P <0.0001), and vs. pioglitazone 0.25 (0.10, 0.40) %
(noninferiority P value 0.27, not shown noninferior). Changes in FPG mirrored
those of A1C (Table). Albiglutide and pioglitazone differed in weight change
direction (Table). Adverse events included more gastrointestinal and injection
Supported by: Korea Drug Development Fund R&D Project (KDDF-201204-03)
For author disclosure information, see page LB66.
ADA-Funded Research
LB16
Clinical Diabetes/Therapeutics
60-LB
62-LB
GSK2374697, a Long-Acting GLP-1 Mimetic: First Use of an AlbudAbв„ў
in Humans—Pharmacokinetics, Pharmacodynamics, Safety, and
ToleraВ­bility in Healthy Volunteers
Durability of Dapagliflozin vs. Glipizide as Add-On Therapies in T2DM
Inadequately Controlled on Metformin: 4-Year Data
STEFANO DEL PRATO, MICHAEL A. NAUCK, SANTIAGO DURГЃN-GARCIA, KATJA
ROHWEDDER, ANETT THEUERKAUF, ANNA MARIA LANGKILDE, SHAMIK J.
PARIKH, Pisa, Italy, Bad Lauterberg, Germany, Seville, Spain, Wedel, Germany,
Cologne, Germany, Mölndal, Sweden, Wilmington, DE
REBECCA J. HODGE, ROBIN L. O’CONNOR-SEMMES, JIANG LIN, JACK P. CHISM,
SUSAN M. ANDREWS, JAMES R. GADDY, DEREK J. NUNEZ, Research Triangle
Park, NC
GSK2374697, a GLP-1 mimetic, is a recombinant fusion protein consisting
of exendin-4 fused to an AlbudAbв„ў, a small (~14 kDa) human antibody light
chain variable domain that reversibly binds to albumin. We assessed the
pharmacokinetics, pharmacodynamics, and safety/tolerability of GSK2374697
in normal and obese healthy volunteers, in the first evaluation of an AlbudAb
in humans. In this double-blind (sponsor unblinded), randomized, placebocontrolled study, 82 subjects (18 placebo, 64 GSK2374697, 19-65 years, BMI
19.2-33.9 kg/m2 and obese BMI 30.6-38.4 kg/m2 received escalating doses
of GSK2374697 or placebo (subcutaneous injections into the abdomen) in
sequential cohorts (C) as follows: Single doses on Day 1 C1: 0.1mg, C2: 0.2mg,
C3: 0.5mg, C4: 1.0mg, C5: 2.0mg, C6: 4.0mg, Divided doses on Days 1, 4, and 7:
C7: 4.0mg as 1mg + 1mg + 2mg, C8: 6.0mg as 2mg + 2mg + 2mg, C9: same as
C8 in subjects with higher BMI.
The median (range) plasma half-life of GSK2374697 was 6.3 d (4-22), median
(range) Tmax was 57 h (12-108), and plasma exposure increased with dose.
Significant reductions in average plasma glucose (doses ≥2mg) and insulin
(doses ≥1mg) were observed following a mixed meal challenge 6/12 days after
single/divided doses (p<0.05, compared to placebo, ANCOVA). GSK2374697
single doses (≥2mg) significantly reduced gastric emptying (measured using
acetaminophen PK).
The most common drug-related adverse events were decreased appetite,
nausea, vomiting, constipation, injection site reactions, diarrhea and dizziness.
The incidence and severity of nausea and vomiting was reduced considerably
when doses were divided compared to single dose administration.
In conclusion, early PK/PD of GSK2374697 supports at least once-weekly
dosing with an acceptable safety/tolerability profile.
Dapagliflozin (DAPA), a selective SGLT2 inhibitor, reduces hyperglycemia
in an insulin-independent manner by increasing urinary glucose excretion.
In a randomized, double-blind trial of DAPA (≤10 mg/d, n=406) vs. glipizide
(GLIP; ≤20 mg/d, n=408) as add-on to metformin (median 2000 mg/d) in T2DM
(NCT00660907, baseline HbA1c 7.72%), DAPA was non-inferior to GLIP in
HbA1c change at 52 weeks (primary endpoint, both в€’0.52%), produced weight
loss and reduced hypoglycemia (hypo). Here we report 4-year data from this
study, the longest duration of therapy studied for any SGLT2 inhibitor to date.
161 DAPA vs. 141 GLIP patients completed Year 4. Effect of therapy on HbA1c
attenuated over time in both groups, but DAPA showed more persistent benefits
vs. GLIP up to Year 4 (change from baseline of в€’0.10 vs. +0.20%): treatment
difference в€’0.30% (95% CI: в€’0.51, в€’0.09). Sustained and stable weight loss
was observed with DAPA vs. weight gain with GLIP (в€’3.95 vs. +1.12 kg):
difference в€’5.07 kg (95% CI: в€’6.21, в€’3.93). Mean systolic BP was reduced with
DAPA but not with GLIP: difference в€’3.7 mmHg (95% CI: в€’5.9, в€’1.4). Rate of
patients with hypo was ~10-fold less with DAPA (5.4%) vs. GLIP (51.5%): most
patients with hypo first presented in Year 1. All major hypos (n=3) were with
GLIP. There were no discontinuations due to hypo with DAPA. Overall rates of
AEs and SAEs were similar between groups. Discontinuation due to AEs was
13.3% for DAPA vs. 11.3% for GLIP. Proportion of patients with UTI was 13.5%
for DAPA vs. 9.3% for GLIP (upper UTI: 1 DAPA vs. 3 GLIP patients). Genital
infections (GenI) occurred in 14.3 vs. 2.9% of patients. Most patients with UTI/
GenI first presented in Year 1. The majority of events were of mild/moderate
intensity and resolved with standard treatment. UTI/GenI were more common
in women. In summary, DAPA demonstrated sustained metabolic benefits
including stable weight loss and low rates of hypo compared with GLIP over 4
years. Therapy was well-tolerated, with no new safety signals identified.
Supported by: Bristol-Myers Squibb/AstraZeneca
Clinical Therapeutics/New Technology—
Oral Agents
63-LB
Imeglimin: A New Antidiabetic Agent that Provides Added Benefit to
DPP-4 Inhibitor Therapy
61-LB
PASCALE FOUQUERAY, CLIFFORD J. BAILEY, VALDIS PIRAGS, MICHAELA
DIAMANT, GUNTRAM SCHERNTHANER, HAROLD E. LEBOVITZ, SILVIO E.
INZUCCHI, Lyon, France, Birmingham, United Kingdom, Amsterdam, Netherlands,
Vienna, Austria, New York, NY, New Haven, CT
Pitavastatin for the Delay or Prevention of Diabetes Development in
Individuals With Impaired Glucose Tolerance
MASATO ODAWARA, TSUTOMU YAMAZAKI, JUNJI KISHIMOTO, CHIKAKO
ITO, MITSUHIKO NODA, YASUO TERAUCHI, TERUO SHIBA, HIROJI KITAZATO,
KOJI MAEMURA, KAZUYUKI TOBE, YASUHIKO IWAMOTO, YASUO AKANUMA,
TAKASHI KADOWAKI, THE J-PREDICT STUDY INVESTIGATORS, Tokyo, Japan,
Fukuoka, Japan, Hiroshima, Japan, Kanagawa, Japan, Nagasaki, Japan, Toyama,
Japan
This 12-week study assessed the efficacy and tolerability of imeglimin as
add-on therapy to sitagliptin in type 2 diabetes patients inadequately controlled
with sitagliptin monotherapy.
This was a multi-center, randomized, double-blind, placebo-controlled,
parallel-group study of imeglimin (1,500 mg BID) or placebo added to
sitagliptin (100 mg QD) in 170 patients with type 2 diabetes (mean age, 56.8
years; 52.9% male; BMI, 32.2 kg/m2) who were inadequately controlled with
sitagliptin alone (A1C ≥ 7.5%) during a 12-week run-in period. The primary
efficacy endpoint was change in A1C from baseline vs. placebo; secondary
endpoints included corresponding changes in fasting plasma glucose (FPG), %
A1C responders, and certain non-glycemic parameters.
Imeglimin-sitagliptin reduced A1C (LS mean) from baseline (8.5%) by 0.60%
compared with an increase of 0.12% with placebo (P <0.001), for a placeboadjusted decrease of 0.72% with imeglimin. The corresponding changes in
FPG were a decrease of 0.80 mmol/L with imeglimin vs. a decrease of 0.19
mmol/L with placebo (P =0.014). 54.3% of subjects achieved a decrease in
A1C ≥ 0.5% with imeglimin vs. 21.6% with placebo (P <0.001), and 19.8% of
subjects receiving imeglimin achieved an A1C ≤ 7% compared with placebo
(1.1%), (P =0.004). Sitagliptin-imeglimin was generally well tolerated with
a comparable safety profile to the sitagliptin-placebo group and no related
treatment-emergent adverse events.
Imeglimin demonstrated incremental efficacy as an add-on therapy to
sitagliptin, with comparable tolerability to sitagliptin-placebo, highlighting the
potential for imeglimin to complement the efficacy of oral anti-hyperglycemic
treatments.
Although statin therapy is known to reduce cardiovascular risk, trial data and
meta-analyses suggest that statins may also increase the risk of development
of diabetes. However, in those trials, data were analyzed retrospectively, and
the diagnostic criteria of diabetes differed. Thus the effect of statins on the
incidence of diabetes has not been clearly defined. To clarify this issue, we
performed the Japan Prevention Trial of Diabetes by Pitavastatin in Patients
with Impaired Glucose Tolerance (J-PREDICT) study, which was a prospective
randomized, controlled trial evaluating the effect of pitavastatin on the
development of diabetes.
Of 8,472 patients who underwent screening, 1,269 individuals with impaired
glucose tolerance (IGT) were randomized to either the pitavastatin group
(lifestyle modification and pitavastatin [1-2 mg/day]) or the control group
(lifestyle modification only). Every six months, a 75-g oral glucose tolerance
test was performed with other standard laboratory tests. The primary outcome
was cumulative incidence of diabetes, as determined by a 2-h plasma glucose
≥200 mg/dl or a fasting plasma glucose ≥126 mg/dl measured at least once.
The diabetes incidence rates for the pitavastatin and control groups were
163 and 186 cases per 1,000 person-years, respectively; the hazard ratio for
progression from IGT to diabetes in the pitavastatin group was 0.82 (95% CI:
0.68-0.99; P = 0.041). Even in any subgroups, pitavastatin did not accelerate
the incidence, unlike the effects of statins in previous reports. Pitavastatin in
combination with lifestyle modification was associated with a lower incidence
of diabetes than was lifestyle modification alone in Japanese patients with
IGT. Statins are now used with the understanding that a slightly increased risk
of diabetes is outweighed by cardiovascular benefits of the drugs. However,
based on our results, it may be necessary to reconsider whether all statins
really increase the risk of developing diabetes.
Supported by: Waksman Foundation of Japan, Inc.; Kowa Pharmaceuticals Co., Ltd.
For author disclosure information, see page LB66.
ADA-Funded Research
LB17
Clinical Diabetes/Therapeutics
64-LB
Overall AE rates were 73%, 78%, and 78% with CANA 100 and 300 mg and
GLIM, and serious AE rates were 10%, 10%, and 14%; discontinuations due
to AEs were low across groups. Genital mycotic infection rates were higher
with CANA (pooled) than GLIM (women, 15% vs. 3%; men, 9% vs. 2%). Higher
rates of osmotic diuresis-related AEs (6%, 7%, 2%) and UTI (11%, 9%, 7%)
were seen with CANA 100 and 300 mg vs. GLIM. Rates of these AEs were
generally lower in the 52-wk extension vs. core period. A larger decrease in
eGFR was seen with GLIM (6%) than CANA (~1-3%) at Wk 104. In summary,
CANA showed durable glycemic improvements vs. GLIM and was generally
well tolerated in subjects with T2DM on MET over 104 wks.
A Euglycemic Clamp Pilot Study Assessing the Effects of the Glucagon
Receptor Antagonist LY2409021 on 24-h Insulin Requirement in Patients
With T1DM
CHRISTOF M. KAZDA, PARAG GARHYAN, YING DING, RONAN P. KELLY, THOMAS
A. HARDY, CHRISTOPH KAPITZA, Neuilly-sur-Seine, France, Indianapolis, IN,
Singapore, Singapore, Neuss, Germany
Recent research shows that blocking glucagon action prevents lethal
metabolic effects seen in mice with type 1 diabetes mellitus (T1DM).
LY2409021 (LY), a potent, selective human glucagon receptor antagonist, is
being investigated as a treatment for T2DM. To test its effects in T1DM, we
assessed whether single oral doses of LY could result in clinically meaningful
reductions of the 24-hour insulin requirement. Twenty T1DM patients with a
mean age of 43.0 years (SD, 10.3 years), a mean diabetes duration of 19.0 years
(SD, 13.8 years), and a mean baseline hemoglobin A1c of 7.6% (SD, 0.7%) had
euglycemia (100 mg/dL) maintained overnight by a glucose-controlled insulin
infusion system (Biostator) after usual insulin regimens were discontinued. On
Day 1, euglycemia was maintained using variable intravenous insulin infusion
and standardized meals. These regimens were readministered on Day 2, but
patients, randomized 1:2:2, also received a placebo or a 100-mg or 300-mg
single dose of LY before breakfast. The placebo-corrected 24-hour insulin
dose needed to maintain euglycemia was reduced by a mean of 17.0% (95%
confidence interval [CI], -33.7% to -0.4%; P=.046) and a mean of 19.6% (95%
CI,-35.0% to -4.3%; P=.019) in 100-mg and 300-mg dose groups, respectively.
Group mean glucose values were well matched and maintained near euglycemia
throughout the clamp procedure. Although LY led to an expected 2- to 3-fold
dose-dependent increase in plasma glucagon levels, no significant changes
from placebo values were observed for other pharmacodynamic parameters,
including levels of glucagon-like peptide-1 (total and active), C-peptide, lipids,
and ОІ-hydroxybutyrate. No clinically significant differences between LY and
placebo groups were observed in hypoglycemia or adverse event frequency
during and after the clamp procedure. Results suggest glucagon antagonism
can reduce insulin requirements in T1DM.
Supported by: Janssen Research & Development, LLC.
66-LB
Durability of the Efficacy and Safety of Alogliptin Compared to Glipizide
Over 2 Years When Used in Combination With Metformin
STEFANO DEL PRATO, RICCARDO CAMISASCA, CRAIG WILSON, PENNY FLECK,
Pisa, Italy, London, United Kingdom, Deerfield, IL
This 3-arm, multicenter, randomized, double-blind, active-controlled study
evaluated the durability of the efficacy and safety of alogliptin (ALO) compared
to glipizide in combination with metformin (MET) in type 2 diabetic patients
inadequately controlled on stable-dose MET. The duration of the study was
104 weeks. The treatment arms were: ALO 12.5 mg QD + MET (ALO 12.5)
(n=880), ALO 25 mg QD + MET (ALO 25) (n=885), and glipizide 5 mg titrated
to a maximum of 20 mg + MET (GLIP) (n=874). The primary efficacy endpoint
was least square mean change from baseline in HbA1c (A1c) at 104 weeks.
The majority of patients were white (62.3%); 50.3% were women. Mean age
was 55.4 years; body mass index, 31 kg/m2; diabetes duration, 5.5 years; and
baseline A1c, 7.6%. Reductions in A1c at Week 104 were ‑0.68%, ‑0.72%, and
-0.59% for ALO 12.5, ALO 25, and GLIP, respectively. More patients achieved
an A1c ≤7% at Week 104 with ALO 25 (48.5%) vs. GLIP (42.8%) (P=0.004);
the proportion for ALO 12.5 was 45.6% (not significant vs. GLIP). Changes in
fasting plasma glucose at Week 104 were -0.9 mg/dL for ALO 12.5, -3.2 mg/
dL for ALO 25, and 5.4 mg/dL for GLIP (P<0.001 for both ALO vs. GLIP). Mean
weight changes at Week 104 were ‑0.68, ‑0.89, and 0.95 kg for ALO 12.5, ALO
25, and GLIP, respectively (P<0.001 for both ALO decreases vs. GLIP). More GLIP
patients (23.2%) experienced ≥1 hypoglycemic event than ALO 12.5 (2.5%) or
ALO 25 (1.4%) patients; severe hypoglycemia occurred in six GLIP, one ALO
12.5, and no ALO 25 patients. Pancreatitis occurred in one ALO 25 patient and
three GLIP patients. Numbers of patients experiencing ≥1 adverse event or an
event leading to treatment discontinuation were similar across the 3 groups.
Eleven deaths occurred: 3 in the ALO 12.5 group, 3 in the ALO 25 group, and 5
in the GLIP group. In summary, alogliptin efficacy was sustained through 104
weeks. The safety profile was similar among the treatment arms, although
considerably lower incidences of hypoglycemia were observed in the ALO dose
groups.
Supported by: Eli Lilly and Company
65-LB
Canagliflozin (CANA) Demonstrates Durable Glycemic Improvements
Over 104 Weeks versus Glimepiride (GLIM) in Subjects With Type 2
Diabetes Mellitus (T2DM) on Metformin (MET)
WILLIAM T. CEFALU, LAWRENCE A. LEITER, KUN-HO YOON, GISLE LANGSLET,
PABLO ARIAS, JOHN XIE, DAINIUS A. BALIS, DAWN MILLINGTON, FRANK
VERCRUYSSE, WILLIAM CANOVATCHEL, GARY MEININGER, Baton Rouge, LA,
Toronto, ON, Canada, Seoul, Republic of Korea, Oslo, Norway, Santa Fe, Argentina,
Raritan, NJ, Beerse, Belgium
The 104-wk efficacy and safety of CANA (longest follow-up to date), an SGLT2
inhibitor, were assessed in this randomized, double-blind study. Subjects with
T2DM on MET (N = 1450; mean age, 56 y; A1C, 7.8%; FPG, 166 mg/dL; BMI, 31
kg/m2; eGFR, 90 mL/min/1.73 m2) received CANA 100 or 300 mg or GLIM (up
to 6 or 8 mg/d) during a 52-wk core period followed by a 52-wk extension (n =
1050). At Wk 104, both CANA doses reduced A1C, FPG, body weight, systolic
BP, and triglycerides vs. GLIM, with HDL-C and LDL-C increases that were
stable from Wk 26 to Wk 104. Fewer subjects had hypoglycemia events with
CANA 100 and 300 mg than GLIM (7%, 8%, 41%). The coefficient of durability
(rate of A1C rise from Wk 26 to Wk 104) was lower with CANA (0.16% both
doses) than GLIM (0.37%).
67-LB
A Novel Antidiabetic Drug Fasiglifam/TAK-875 Acts as an AgoAllosteric Modulator for FFAR1
CHIORI YABUKI, HIDETOSHI KOMATSU, YOSHIYUKI TSUJIHATA, RISA MAEDA,
RYO ITO, KAE MATSUDA-NAGASUMI, KENSUKE SAKUMA, KAZUMASA
MIYAWAKI, NAOYA KIKUCHI, KOJI TAKEUCHI, YUGO HABATA, MASAAKI MORI,
Fujisawa, Japan
The selective FFAR1/GPR40 agonist fasiglifam (TAK-875), an antidiabetic
drug in phase 3 development, potentiates insulin secretion in a glucosedependent manner by activating FFAR1 expressed in pancreatic ОІ cells.
Fasiglifam significantly improved glycemic control in diabetic patients with
a low risk of hypoglycemia in phase 2 studies. However, precise mechanism
of the involvement of endogenous free fatty acids (FFAs) on the efficacy of
fasiglifam in vivo is not fully understood. Here, we show that fasiglifam acts
as a positive allosteric modulator with partial agonist activity for FFAR1. In
a Ca2+ influx assay using CHO-hFFAR1 cells, the EC50 of Оі-linolenic acid (ОіLA), an FFAR1 endogenous ligand, was shifted from 5.39 ОјM to 1.07 ОјM in
the presence of fasiglifam (1 ОјM), indicating positive cooperativity between
fasiglifam and FFA. In mouse insulinoma MIN6 cells and mouse islets, the
combination of fasiglifam (10 ОјM) and Оі-LA (100 ОјM) dramatically potentiated
glucose-induced insulin secretion (Fas; 1.8 fold, Оі-LA; 3.5 fold, Fas+Оі-LA; 12.2
fold increase vs. control in mouse islets), while the insulinotropic activities
of these agonists were completely abolished in FFAR1-/- mouse islets.
Furthermore, reduction of plasma FFA levels with the lipolysis inhibitor
acipimox (30 mg/kg) caused significant suppression of the insulinotropic effect
of fasiglifam (10 mg/kg) in N-STZ-1.5 rats, suggesting that plasma FFAs affect
insulin release by fasiglifam in vivo. Point mutations of FFAR1 differentially
affected the Ca2+ influx activities of fasiglifam and Оі-LA, further supporting
that these agonists utilize distinct binding sites. Our results indicate that
For author disclosure information, see page LB66.
ADA-Funded Research
LB18
Clinical Diabetes/Therapeutics
fasiglifam is an ago-allosteric modulator for FFAR1 that exerts its potent
pharmacological effects by acting cooperatively with FFAs, offering greater
efficacy in the presence of endogenous ligands. These findings contribute to
our understanding of fasiglifam as an attractive antidiabetic drug with a novel
mechanism of action.
cholesterol and small decreases in triglyceride levels were observed with
EMPA vs. PBO.
In conclusion, in a pooled analysis of data from four Phase III trials, 24
weeks’ treatment with EMPA 10 mg or 25 mg provided clinically meaningful
improvements in glycemic parameters, weight, and BP, with positive effects on
uric acid and small effects on lipids.
68-LB
Placebo
Regardless of the Degree of Glycemic Control, Linagliptin (LINA) has
Lower Hypoglycemia Risk than All Doses of Glimepiride (GLIM) at All
Time Points Over a 2-Year Trial
HbA1c (%)†Baseline‡ (SE)
Change from baseline at week 24 (SE)
Difference vs. placebo (95% CI)
BAPTIST GALLWITZ, JULIO ROSENSTOCK, SANJAY PATEL, MAXIMILIAN VON
EYNATTEN, UWE HEHNKE, LUDWIG MEHLBURGER, KLAUS A. DUGI, HANSJUERGEN WOERLE, TГјbingen, Germany, Dallas, TX, Bracknell, United Kingdom,
Ingelheim, Germany
Sulfonylurea (SU)-induced hypoglycemia is a common problem in type
2 diabetes. In a 2-yr, randomized, double-blind study of the DPP-4 inhibitor
LINA 5 mg/d (n=764) vs. the SU GLIM 1-4 mg/d (n=755) in pts uncontrolled by
metformin, LINA provided noninferior reductions in HbA1c to GLIM with a lower
hypoglycemia risk and no weight gain. This exploratory analysis evaluated the
risk for investigator-reported hypoglycemia with GLIM based on dose, over time,
and by HbA1c reduction vs. LINA. Pts randomized to GLIM started at 1 mg. Pts not
achieving FPG ≤110 mg/dL at 4 wks and not at hypoglycemia risk were uptitrated
stepwise to 4 mg. The % pts with hypoglycemia at the maximum GLIM dose was:
1 mg, 45.0%; 2 mg, 50.8%; 3 mg, 36.1%; 4 mg, 27.7%. During the study, the %
pts with hypoglycemia was higher with GLIM vs. LINA (36.1 vs. 7.5%; p<0.0001);
after excluding events during dose escalation (wks 0-16), this difference remained
significant (wks 16-104; 25.8 vs. 5.9%; p<0.0001). At wks 4, 8, 12, 16, and 104,
the % pts with hypoglycemia was higher with GLIM vs. LINA in each quartile of
HbA1c change from baseline (all p<0.0001); the % pts with hypoglycemia was not
increased with greater reductions in HbA1c in either group. In all 4-wk intervals,
the % pts with hypoglycemia was lower with LINA vs. GLIM (Figure). In summary,
LINA was associated with a lower risk for hypoglycemia than GLIM at all times,
all dose levels, and regardless of change in HbA1c.
Empagliflozin
10 mg
Empagliflozin
25 mg
8.02 (0.03) 7.98 (0.03)
7.96 (0.03)
-0.08 (0.03) -0.70 (0.03)
-0.76 (0.03)
-0.62
-0.68
(-0.69, -0.55)*** (-0.75, -0.61)***
FPG (mg/dL)†Baseline (SE)
Change from baseline at week 24 (SE)
Difference vs. placebo (95% CI)
153.7 (1.3)
7.4 (1.0)
152.6 (1.2)
152.6 (1.2)
в€’20.5 (1.0)
в€’23.2 (1.0)
-27.9
-30.6
(-30.7, -25.1)*** (-33.4, -27.8)***
Body weight (kg)†Baseline (SE)
Change from baseline at week 24 (SE)
Difference vs. placebo (95% CI)
78.03 (0.66)
-0.24 (0.09)
78.77 (0.65)
79.10 (0.66)
-2.05 (0.09)
-2.25 (0.09)
-1.81
-2.01
(-2.05, -1.57)*** (-2.25, -1.76)***
SBP (mmHg)†Baseline (SE)
Change from baseline at week 24 (SE)
Difference vs. placebo (95% CI)
128.6 (0.5)
-0.5 (0.4)
129.6 (0.5)
-3.9 (0.4)
-3.4
(-4.4, -2.3)***
129.0 (0.5)
-4.3 (0.4)
-3.8
(-4.9, -2.8)***
DBP (mmHg)†Baseline (SE)
Change from baseline at week 24 (SE)
Difference vs. placebo (95% CI)
78.0 (0.3)
-0.6 (0.2)
78.7 (0.3)
-1.8 (0.2)
-1.2
(-1.9, -0.5)***
78.3 (0.3)
-2.0 (0.2)
-1.5
(-2.1, -0.8)***
SBP (mmHg) in patients with uncontrolled BP at baseline В¶
Baseline (SE)
136.3 (0.6)
136.9 (0.6)
137.4 (0.5)
Change from baseline at week 24 (SE)
-2.5 (0.5)
-7.0 (0.5)***
-7.7 (0.5)***
DBP (mmHg) in patients with uncontrolled BP at baseline В¶
Baseline (SE)
82.4 (0.3)
83.1 (0.3)
82.6 (0.3)
Change from baseline at week 24 (SE)
-1.9 (0.3)
-3.5 (0.3)***
-3.7 (0.3)***
Total cholesterol (mmol/L)В§
Baseline (SE)
4.70 (0.04)
4.67 (0.04)
4.70 (0.04)
Change from baseline at week 24 (SE)
0.04 (0.02)
0.11 (0.02)
0.16 (0.02)***
HDL cholesterol (mmol/L)В§
Baseline (SE)
1.26 (0.01)
1.26 (0.01)
1.27 (0.01)
Change from baseline at week 24 (SE)
0.00 (0.01)
0.07 (0.01)*** 0.07 (0.01)***
LDL cholesterol (mmol/L)В§
Baseline (SE)
2.62 (0.03)
2.57 (0.03)
2.57 (0.03)
Change from baseline at week 24 (SE)
0.02 (0.02)
0.08 (0.02)
0.10 (0.02)**
Triglycerides (mmol/L)В§
Baseline (SE)
1.86 (0.04)
1.95 (0.05)
1.96 (0.07)
Change from baseline at week 24 (SE)
0.03 (0.04) -0.11 (0.04)*
-0.02 (0.04)
Uric acid (Ојmol/L)В§
Baseline (SE)
321.44 (2.98) 321.81 (2.89)
322.35 (2.96)
Change from baseline at week 24 (SE)
1.03 (1.83) -28.95 (1.82)*** -29.55 (1.83)***
Adjusted means based on ANCOVA with last observation carried forward imputation; values on
rescue medication were excluded from analysis of HbA1c, FPG, weight and BP but included in
analysis of lipid parameters and uric acid.
†Full analysis set (all randomized and treated patients who had a baseline HbA value).
1c
‡Inclusion criteria: HbA1c ≥7.0% to ≤10.0%.
¶Patients with uncontrolled BP (SBP ≥130 mmHg or DBP ≥80 mmHg) at baseline.
§Treated set (all patients treated with at ≥1 dose of randomized study medication).
*p<0.05 vs. placebo; **p<0.01 vs. placebo; ***p<0.001 vs. placebo.
Supported by: Boehringer Ingelheim Pharmaceuticals, Inc.
69-LB
Empagliflozin Improves Glycemic Parameters and Cardiovascular
Risk Factors in Patients With Type 2 Diabetes (T2DM): Pooled Data
from Four Pivotal Phase III Trials
THOMAS HACH, JOHN E. GERICH, AFSHIN SALSALI, GABRIEL KIM, STEFAN
HANTEL, HANS J. WOERLE, ULI C. BROEDL, Ingelheim, Germany, Rochester, NY,
Biberach, Germany
We analyzed pooled data from 2477 patients with T2DM (mean [SD] age
55.6 [10.2] years, HbA1c 7.99 [0.85], BMI 28.7 [5.5]) from four randomized,
placebo-controlled Phase III trials that investigated empagliflozin (EMPA) 10
mg or 25 mg given for 24 weeks as monotherapy, add-on to metformin (MET),
add-on to MET + SU, or add-on to pioglitazone В± MET. Effects on HbA1c, fasting
plasma glucose (FPG), weight, systolic and diastolic blood pressure (SBP and
DBP) were evaluated in the full analysis set (placebo [PBO]: n=825, EMPA 10
mg: n=831, EMPA 25 mg: n=821). Effects on lipids and uric acid were evaluated
in all treated patients (PBO: n=825, EMPA 10 mg: n=830, EMPA 25 mg: n=822).
Effects on SBP and DBP were also evaluated in patients with uncontrolled BP
(SBP ≥130 mmHg or DBP ≥80 mmHg) at baseline (PBO: n=501, EMPA 10 mg:
n=517, EMPA 25 mg: n=506).
EMPA significantly reduced HbA1c, FPG, weight, SBP, DBP and uric acid
at week 24 vs. PBO. Reductions in SBP and DBP were more pronounced in
patients with uncontrolled BP at baseline. Small increases in HDL- and LDL-
Supported by: Boehringer Ingelheim Pharmaceuticals, Inc.
For author disclosure information, see page LB66.
ADA-Funded Research
LB19
Clinical Diabetes/Therapeutics
70-LB
FFM-1.min-1.nM-1, p=ns). Conclusions: in T2D patients empagliflozin lowers
fasting and postprandial glycemia by (a) increasing total glucose removal
despite a compensatory increase in EGP, (b) improving Гџ-cell function, and (c)
shifting substrate utilization from glucose to lipid.
Exploring the Potential of Dapagliflozin in Type 1 Diabetes: Phase 2a
Pilot Study
ROBERT R. HENRY, JULIO ROSENSTOCK, ALEXANDROS-GEORGIOS CHALAВ­
MANDARIS, SREENEERANJ KASICHAYANULA, ALLYSON BOGLE, STEVEN C.
GRIFFEN, San Diego, CA, Dallas, TX, Braine-l’Alleud, Belgium, Princeton, NJ
Supported by: Boehringer Ingelheim Pharma GmbH & Co. KG
72-LB
Insulin therapy for type 1 diabetes (T1D) is associated with weight gain and
is often insufficient in maintaining glycemic control. Dapagliflozin (DAPA), an
insulin-independent sodium glucose cotransporter 2 inhibitor that increases
urinary glucose excretion, has shown antihyperglycemic efficacy in type 2
diabetes. This 2-week randomized, double-blind, placebo-controlled, Phase 2a
study evaluated DAPA added to insulin in patients with suboptimally controlled
T1D. Adult patients on stable insulin with HbA1c 7-10% (baseline mean 8.5%)
were randomized to receive DAPA (1, 2.5, 5, or 10 mg) or placebo once daily for
14 days (Days -3 to 7 as inpatients). DAPA PK/PD, including continuous glucose
monitoring (CGM) and 24-hour urine glucose, was assessed at Day 7. Seventy
patients were randomized to treatment; 62 (88.6%) completed the trial. As
expected, there was a dose-dependent increase in urine glucose with DAPA.
CGM data suggested a potential for reduced glycemic levels and diminished
glycemic variability with DAPA. Marked reductions in total daily insulin dosing
at Day 7 were reported for DAPA 5 mg (-19%) and 10 mg (-16%). Hypoglycemia
was common in all treatment groups; 1 event (DAPA 10 mg) was major and
led to discontinuation. The incidence of AEs was 38.5% to 61.5%; there was
1 non-treatment-related serious AE (DAPA 5 mg) and no deaths. DAPA was
generally well tolerated in this T1D population. Further studies to determine
the potential benefit of DAPA as treatment of T1D are warranted.
Novel Mechanism of Luseogliflozin, SGLT2 Inhibitor, Induced BeneВ­
ficial Serum Uric Acid-Lowering Effect
YUKIHIRO CHINO, HIROSHI ARAKAWA, YOSHISHIGE SAMUKAWA, SOICHI
SAKAI, JUN-ICHI YAMAGUCHI, TAKEO NAKANISHI, IKUMI TAMAI, Kanazawa,
Japan, Tokyo, Japan
Sodium glucose co-transporter 2 (SGLT2) inhibitors have known as lowering
serum uric acid (UA) levels likely a class effect. This is the first report to
elucidate a possible mechanism of the serum UA-lowering effect by SGLT2
inhibitors. Initially, we analyzed the laboratory data of healthy subjects and
patients with type 2 diabetes mellitus dosed with Luseogliflozin. It was found
that serum UA levels decreased to 0.5-1.6 mg/dL (0.5-25 mg single) and 0.4-0.8
mg/dL (0.5-10 mg daily for 12 weeks), respectively, from the baseline level (4.86.4 mg/dL). In healthy subjects, a negative correlation was observed between
serum UA and urinary UA levels, and the renal UA clearance increased after
dose of Luseogliflozin. These results suggest that the decrease of serum
UA is due to the increased renal UA clearance. On single dosing in healthy
subjects, UA excretion reached a plateau at a low dose of 1 mg. The increase
of urinary UA excretion coupled to that of urinary glucose (Glc) excretion, but
not to the pharmacokinetics of Luseogliflozin. From these findings, we focused
attention on Glc which concentrated in urine and Glc transporter 9 isoform 2
(GLUT9-iso2, SLC2A9) which expresses in the apical membrane of proximal
tubule epithelial cells and transports both of UA and Glc. We examined the
effect of Glc on the efflux of 14C-UA by Xenopus oocytes expressing GLUT9iso2. As a result, higher Glc concentration of over renal threshold of Glc clearly
stimulated 14C-UA efflux, suggesting that GLUT9-iso 2 plays an important role
on facilitation of UA secretion by exchanging urinary Glc with intracellular UA
after dosing of Luseogliflozin. Therefore, GLUT9-iso2 could be a main player
of serum UA lowering by SGLT2 inhibitors. In addition, this mechanism may
also explain the relevance in appearance of urinary Glc and declining trend of
serum UA in diabetes.
Placebo + DAPA 1 mg + DAPA 2.5 mg DAPA 5 mg + DAPA 10 mg +
insulin
insulin
+ insulin
insulin
insulin
(n=10 to13) (n=10 to 13) (n=11 to 15) (n=13 to 14) (n=9 to 15)
Hypoglycemia No. pts (%) with
(%)
≥1 event
8 (61.5)
12 (92.3)
9 (60.0)
24 h urine
Baseline, g/24h В± SD 30.7 В± 52.0 6.6 В± 6.5 12.1 В± 12.3
glucose
Day 7, g/24h В± SD
9.0 В± 7.5 48.5 В± 20.8 60.8 В± 38.2
excretion
Mean change from
baseline, g/24h
-21.6
41.9
48.5
(95% CI)
(-54.4, 11.1) (27.6, 56.1) (28.1, 69.0)
11 (78.6)
11.2 В± 10.9
83.6 В± 47.9
10 (66.7)
11.9 В± 14.3
99.7 В± 58
72.4
(47.0, 97.9)
88.8
(55.2, 122.5)
24 h glucose/ Baseline, mg/dL В± SD 174 В± 43
162 В± 30
174 В± 42
174 В± 33
CGM daily
Day 7, mg/dL В± SD
154 В± 41
146 В± 20
164 В± 37
144 В± 51
average
Mean change from
baseline, mg/dL
-20.4
-15.7
-13.9
-29.5
(95% CI)
(-65.4, 24.7) (-38.6, 7.2) (-47.0, 19.1) (-47.2, -11.9)
73-LB
174 В± 44
139 В± 35
Canagliflozin (CANA) Is Effective and Generally Well Tolerated in
Subjects With Type 2 Diabetes Mellitus (T2DM) and Stage 3 Chronic
Kidney Disease (CKD)
-41.3
(-66.8, -15.7)
VINCENT WOO, MELANIE DAVIES, DICK DE ZEEUW, GEORGE BAKRIS, VLADO
PERKOVIC, CRISTIANA GASSMANN-MAYER, UJJWALA VIJAPURKAR, KEITH
USISKIN, GARY MEININGER, Winnipeg, MB, Canada, Leicester, United Kingdom,
Groningen, Netherlands, Chicago, IL, Sydney, Australia, Titusville, NJ, Raritan, NJ
Supported by: Bristol-Myers Squibb and AstraZeneca
The efficacy/safety of the SGLT2 inhibitor, CANA, was assessed by a pooled
analysis in subjects with T2DM from 4 randomized, placebo (PBO)-controlled
studies (Wk 18, 1 study; Wk 26, 3 studies) with an eGFR ≥30 and <60 mL/
min/1.73 m2 (N = 1,085) and in subgroups with eGFR ≥45 and <60 (n = 721)
or ≥30 and <45 mL/min/1.73 m2 (n = 364). CANA 100 and 300 mg reduced
A1C, body weight, and systolic BP versus PBO across populations (Table); A1C
and body weight changes were larger in subjects with eGFR ≥45 than <45
mL/min/1.73 m2. For the pooled CANA group, overall AE rates were higher
than PBO across populations (eGFR ≥30 to <60: 74.7% vs. 70.4%; ≥45: 71.0%
vs. 66.9%; <45: 81.5% vs. 78.4%); serious AE rates were higher with PBO
than CANA and AE-related discontinuation rates were low across populations.
Rates of osmotic diuresis-related AEs (eg, pollakiuria, polyuria) were higher
with CANA than PBO in subjects with eGFR ≥30 and <60 (4.0% vs. 3.7%)
and <45 mL/min/1.73 m2 (4.8% vs. 2.6%). Rates of AEs related to reduced
intravascular volume (eg, postural dizziness, orthostatic hypotension) were
higher with CANA than PBO across populations (eGFR ≥30 to <60: 6.8% vs.
2.6%; ≥45: 5.9% vs. 3.4%; <45: 8.9% vs. 1.7%). Rates of renal-related AEs that
were serious or led to discontinuation were low and similar across groups. In
summary, in subjects with T2DM and Stage 3 CKD, CANA reduced A1C with a
greater effect in subjects with higher eGFR, and was generally well tolerated.
71-LB
Metabolic Response to Sodium-Glucose Transporter 2 (SGLT2)
Inhibition With Empagliflozin in Patients With Type 2 Diabetes (T2D)
ELE FERRANNINI, ELZA MUSCELLI, SILVIA FRASCERRA, SIMONA BALDI,
ANDREA MARI, TIM HEISE, ULI C. BROEDL, HANS-JUERGEN WOERLE, Pisa, Italy,
Padova, Italy, Neuss, Germany, Ingelheim, Germany
SGLT2 inhibitors lower glycemia by enhancing urinary glucose excretion.
The physiologic response to pharmacologically-induced glycosuria has not
been investigated. We studied 66 T2D patients (62В±7 years, BMI=31.6В±4.5 kg/
m2, HbA1c=7.2±0.2%, µ±SD) at baseline, after a single dose (25 mg, StudyI),
and following 4 weeks of treatment with empagliflozin (25 mg/d, StudyII). For
each study, patients received a mixed meal coupled with double-tracer glucose
administration and indirect calorimetry. Compared to baseline, StudyI caused
glycosuria (7.8[4.4] g over 3 hrs of fasting, median[IQR]), which led to an increase
in endogenous glucose production (EGP, 13.8[5.2] to 17.6[4.8] Вµmol.kgFFM-1.
min-1, p<0.0001) matching the glycosuria. These fasting-state changes were
maintained in StudyII. Postmeal glycosuria rose to 29.0[12.5] and 28.2[15.4]
g over 5 hrs in StudyI and II, respectively. Correspondingly, postmeal glucose
AUC (51[11] and 51[10] vs. 57[16] g/dL) and insulin AUC (80[59] and 76[59]
vs. 93[68] nmol/L) dropped, whereas the glucagon response rose (6.5[2.1] and
5.6[1.8] vs. 5.2[1.6] nmol/L) (all p<0.001). While appearance of oral glucose
was unchanged, postmeal EGP was increased (AUC=40[14] and 37[11] vs.
34[11] g, both p<0.01). Tissue glucose disposal (=total glucose disposal minus
glycosuria) was reduced (75[16] and 70[21] vs. 93[18] g, p<0.0001) due to a
decrease in both glucose oxidation and non-oxidative glucose disposal, with
a concomitant rise in lipid oxidation (all p<0.01). Гџ-cell glucose sensitivity
improved (55[35] and 55[39] vs. 44[32] pmol.min-1.m-2.mM-1, p<0.0001),
while insulin sensitivity was unchanged (9.1[6.7] and 8.6[8.0] vs. 8.2[5.8] ml.kg
For author disclosure information, see page LB66.
ADA-Funded Research
LB20
Clinical Diabetes/Therapeutics
Number of episodes per patient,
n (%)
0
1
2
≥3
Intensity of worst episode, n (%)
Mild
Moderate
Severe
Patients with events consistent
with UTI leading to treatment
discontinuation, n (%)
Events consistent with genital
infection
Patients with events consistent
with genital infection, n (%)
Male, n/N (%)
Female, n/N (%)
Patients without history of chronic or
recurrent genital infections, n/N (%)
Patients with history of chronic or
recurrent genital infections, n/N (%)
Number of episodes per patient,
n (%)
0
1
2
≥3
Intensity of worst episode, n (%)
Mild
Moderate
Severe
Patients with events consistent
with genital infections leading to
treatment discontinuation, n (%)
Supported by: Janssen Research & Development, LLC.
74-LB
Empagliflozin (EMPA) Increases Genital Infections But Not Urinary
Tract Infections (UTIs) in Pooled Data from Four Pivotal Phase III
Trials
GABRIEL KIM, JOHN E. GERICH, AFSHIN SALSALI, THOMAS HACH, STEFAN
HANTEL, HANS J. WOERLE, ULI C. BROEDL, Ingelheim, Germany, Rochester, NY,
Biberach, Germany
SGLT2 inhibitors increase urinary glucose excretion. It is important to identify
whether this promotes UTIs and/or genital infections.
Four randomized, placebo-controlled Phase III trials investigated the effect
of EMPA for 24 weeks as monotherapy, add-on to metformin, add-on to
metformin + SU, or add-on to pioglitazone В± metformin in patients with T2DM.
Using pooled data from these trials, which included 2477 patients (mean age
55.6 [SD 10.5] years) treated with EMPA 10 mg (n=830), EMPA 25 mg (n=822)
or PBO (n=825), events consistent with UTI or genital infection were evaluated
using prospectively defined search categories of 67 or 87 preferred terms,
respectively.
The percentage of patients with events consistent with UTI was similar
with PBO and EMPA (8-9%). More patients on EMPA than PBO reported events
consistent with genital infection (4% vs. 1%). Both types of event were more
common in women than men and more common in patients with a history of
UTI or genital infection (table). Most patients who reported an event consistent
with UTI or genital infection experienced only 1 such episode, very few patients
discontinued due to such an event and most events were mild in intensity.
To conclude, in a pooled analysis of data from 2477 patients, EMPA was not
associated with an increased frequency of UTIs, but was associated with an
increased frequency of genital infections compared with PBO.
Events consistent with UTI
Patients with events consistent
with UTI, n (%)
Male, n/N (%)
Female, n/N (%)
Patients without a history of chronic
or recurrent UTIs, n/N (%)
Patients with a history of chronic or
recurrent UTIs, n/N (%)
Placebo
(n=825)
Empagliflozin Empagliflozin
10 mg
25 mg
(n=830)
(n=822)
68 (8.2)
16/424 (3.8)
52/401 (13.0)
77 (9.3)
62 (7.5)
9/463 (1.9) 5/464 (1.1)
68/367 (18.5) 57/358 (15.9)
57/772 (7.4)
66/788 (8.4)
11/53 (20.8)
11/42 (26.2)
757 (91.8)
62 (7.5)
6 (0.7)
0
753 (90.7)
65 (7.8)
10 (1.2)
2 (0.2)
760 (92.5)
56 (6.8)
6 (0.7)
0
57 (6.9)
9 (1.1)
2 (0.2)
62 (7.5)
14 (1.7)
1 (0.1)
55 (6.7)
7 (0.9)
0
1 (0.1)
2 (0.2)
1 (0.1)
6 (0.7)
2/424 (0.5)
4/401 (1.0)
35 (4.2)
30 (3.6)
12/463 (2.6) 5/464 (1.1)
23/367 (6.3) 25/358 (7.0)
5/818 (0.6)
33/826 (4.0)
27/809 (3.3)
1/7 (14.3)
2/4 (50.0)
3/13 (23.1)
819 (99.3)
5 (0.6)
1 (0.1)
0
795 (95.8)
30 (3.6)
3 (0.4)
2 (0.2)
792 (96.4)
25 (3.0)
4 (0.5)
1 (0.1)
5 (0.6)
1 (0.1)
0
24 (2.9)
11 (1.3)
0
20 (2.4)
10 (1.2)
0
1 (0.1)
2 (0.2)
0
Supported by: Boehringer Ingelheim Pharmaceuticals, Inc.
75-LB
Delayed-Release Metformin May Be Suitable for Use in Diabetes
Patients With Renal Impairment that are Contraindicated for Currently
Available Metformin Formulations
RALPH A. DEFRONZO, JOHN B. BUSE, JON MONTELEONE, TERRI KIM, SHARON
SKARE, ALAIN BARON, MARK FINEMAN, San Antonio, TX, Chapel Hill, NC, Cary,
NC, San Diego, CA
We recently uncovered that metformin’s (Met) glucose-lowering effects
are predominantly due to actions on enteroendocrine L-cells which are more
densely populated in the lower bowel and that plasma Met exposure is not
required for efficacy (ADA 2013, #1087-P). Met is contraindicated in patients
with renal impairment due to Met accumulation and associated risk of lactic
acidosis. By targeting a daily dose of 1000 mg delayed-release metformin (Met
DR) directly to the lower bowel of patients with type 2 diabetes, Met exposure
was reduced by 68% relative to a daily dose of 2000 mg immediate release
Met (Met IR). Despite lower Met exposure, Met DR produced a similar glucose
lowering effect as Met IR and increased fasting and postprandial GLP-1 and PYY.
We hypothesized that Met DR may be a viable treatment for diabetic patients
with renal impairment. We used a population PK model based on data from 2
clinical studies (N=44) of Met DR, Met IR, and Met extended-release (Met XR)
to predict Met exposure (AUC0-48) following administration of each formulation
in normal subjects and those with varying degrees of renal impairment (mild
to severe). The median predicted AUCs (ng*h/mL) for 1000 mg daily Met DR in
patients with normal, mild, moderate and severe renal impairment were 4669,
4984, 5524, and 6527. Predicted AUCs (ng*h/mL) were significantly higher for
2000 mg daily Met IR and Met XR (22659 and 20607 with normal renal function
and 31606 and 29074 with severe renal impairment). Thus, in patients with
severe renal impairment, 1000 mg daily Met DR is predicted to result in lower
Met exposure than 2000 mg daily Met IR or Met XR in patients with normal
renal function, while maintaining comparable glucose-lowering efficacy. Met
51/776 (6.6)
11/46 (23.9)
For author disclosure information, see page LB66.
ADA-Funded Research
LB21
Clinical Diabetes/Therapeutics
DR may provide a method to treat renally impaired type 2 diabetic patients
with metformin without increasing the risk of Met associated lactic acidosis.
acarbose group was markedly greater than that in metformin group (fasting
glucagon: -11.4pg/mL vs. -0.5pg/mL; 0.5h postprandial glucagon: 5.7 pg/mL vs.
-10.7pg/mL, respectively. P<0.05).
Conclusion: In newly diagnosed type 2 diabetic patients metformin and
acarbose have similar effect on improving glucose control and decreasing
body weight as monotherapy. It seemed that acarbose may improve islet О± cell
function better than metformin, representing by the greater decrease of fasting
and 0.5h postprandial glucagon. Although the improvement of О”I30/О”G30 can
decrease postprandial glucagon, further studies are needed to explore the
related pathophisiology mechanism.
76-LB
Efficacy and Safety of Canagliflozin (CANA) in Older Subjects With
Type 2 Diabetes Mellitus (T2DM)
BRUCE W. BODE, ALAN SINCLAIR, STEWART HARRIS, UJJWALA VIJAPURKAR,
CRISTIANA GASSMANN-MAYER, ALBERT FUNG, WAYNE SHAW, KEITH USISKIN,
MEHUL DESAI, GARY MEININGER, Atlanta, GA, Luton, United Kingdom, London,
ON, Canada, Raritan, NJ, Titusville, NJ
The efficacy and safety of CANA, an SGLT2 inhibitor, were evaluated
using pooled data in subjects with T2DM from 4 randomized, placebo (PBO)controlled, 26-week studies (N = 2,313) and analyzed by age: <65 y (n = 1,868;
male, 49.1%; mean age, 52.8 y; A1C, 8.0%; body weight, 90.1 kg; eGFR, 90.8
mL/min/1.73 m2) or ≥65 y (n = 445; male, 51.5%; mean age, 69.3 y; A1C, 7.9%;
body weight, 85.1 kg; eGFR, 76.9 mL/min/1.73 m2). CANA 100 and 300 mg
reduced A1C, body weight, and systolic BP relative to PBO in subjects <65
and ≥65 y (Table); similar lipid changes were seen in both age groups. Overall
adverse event (AE) rates were similar with CANA 100 and 300 mg and PBO
in subjects <65 y (59.9%, 59.0%, 58.9%) and ≥65 y (61.0%, 60.4%, 61.3%).
Serious AE and AE-related discontinuation rates were similar with CANA
100 and 300 mg and PBO in subjects <65 y (serious AEs: 2.5%, 2.5%, 3.3%;
AE-related discontinuations: 3.3%, 3.2%, 2.8%), and higher with CANA 100
mg than CANA 300 mg or PBO in subjects ≥65 y (serious AEs: 6.9%, 3.4%,
3.6%; AE-related discontinuations: 8.8%, 5.4%, 4.4%). As in subjects <65 y,
those ≥65 y who received CANA had higher rates than PBO of genital mycotic
infections in women and men and osmotic diuresis-related AEs; rates of AEs
related to reduced intravascular volume were low in both age groups. UTI
and renal-related AE rates were similar across groups in subjects ≥65 y. In
summary, both CANA doses provided reductions in A1C and body weight and
were generally well tolerated in older subjects with T2DM.
Resveratrol Synergy in Pre-Diabetes
78-LB
JANIE LIPPS, SCOTT HAGAN, MICHELLE CLARK, DIANNE DAVIS, LIBBY STONE,
LIBBY SURVANT, WANDA SNEAD, KEVIN NISWENDER, Nashville, TN
Impaired glucose tolerance (IGT) and fasting hyperglycemia (FH) are risk
factors for diabetes. Caloric restriction sensitizes to insulin, in part via SIRT1.
Resveratrol (Res) is a SIRT1 activator shown to increase insulin sensitivity. The
utility of resveratrol in metabolic disease has been limited by the large doses
required (>1-6 g/d) and oral bioavailability. Leucine (Leu) and metabolites
such as ОІ-Hydroxy ОІ-Methylbutyrate (HMB) also stimulate SIRT1 activity.
Resveratrol in combination with either leucine or HMB left-shifts in vitro
SIRT1 activity dose-response curves and reduces the EC50 from micromolar
to nanomolar concentrations. In rodents resveratrol-leucine (ResLeu) and
resveratrol-HMB (ResHMB) improved metabolic function.
Humans with FH (100-125 mg/dL) or IGT (75 g OGTT, 2 hour between 140199 mg/dL) were randomized to receive resveratrol (50 mg)/leucine (1.11 g)
(ResLeu, n=13), resveratrol (50 mg)/HMB (500 mg)(ResHMB, n=11) or placebo
(n=12) twice daily (bid) in a blinded fashion. Primary outcomes were derived
from change in glucodynamic responses on 75 g OGTT from baseline to 28 days
of treatment: change glucose area under the curve (AUC), insulin AUC, and
disposition index (0-120 insulin AUC/0-120 glucose AUC * 1/fasting insulin).
Fasting plasma IRISIN levels were also assessed by commercial ELISA assay.
Relative to placebo, ResHMB significantly improved the change in glucose
AUC (2384 placebo vs. -273 HMBRes relative units; p=0.001). ResLeu
significantly lowered the change in insulin AUC relative to placebo (2871
placebo vs. -3803 LeuRes; p=0.02) while ResHMB trended to do so (1037;
p=0.09). Finally, relative to placebo, both LeuRes (p=0.03) and HMBRes (p=0.01)
generated larger changes in disposition index. Finally, while neither placebo
nor HMBRes changed fasting irisin levels, LeuRes increased circulating irisin
by nearly 50% from 340В±60 to 502В±92 ng/mL (p=0.02). Thus, capitalizing on
synergistic properties of HMB and Leu with resveratrol may be an attractive
neutraceutical strategy to improve metabolism.
Supported by: NuSirt Sciences, Inc.
Clinical Therapeutics/New Technology—
Pharmacologic Treatment of Complications
79-LB
FG-4592, a Novel Oral Hypoxia Inducible Factor (HIF) Stabilizer, Raises
Hemoglobin (Hb) in Diabetic Subjects With Anemia of Chronic Kidney
Disease (CKD)
Supported by: Janssen Research & Development, LLC.
77-LB
ANATOLE BESERAB, ROBERT LEONG, MARIETTA FRANCO, BRIAN K. ROBERTS,
TYSON LEE, THOMAS B. NEFF, KIN-HUNG PEONY YU, Detroit, MI, San Francisco,
CA
Effect of Metformin and Acarbose in Islet a Cell Function in Overweight
and/or Obese Patients With Newly Diagnosed Type 2 Diabetes
WEIPING SUN, GUOHUA LI, LIZHEN LIAO, YING WANG, Xiangtan, China
Diabetes is a leading cause of CKD. Anemia of CKD is associated with
lower quality of life and increased rate of progression to ESRD and death, yet
is undertreated outside the dialysis setting due to the cost, inconvenience,
and safety concerns associated with use of erythropoiesis-stimulating
agents (ESAs). FG-4592 is an oral HIF stabilizer that increases endogenous
erythropoietin and utilization of iron (Fe). We report the effects of FG‑4592
on Hb, total cholesterol (TC), and blood pressure (BP) in a subset of diabetic
patients (n=107 [74%], majority T2DM) from an open-label, Phase 2 study of
145 adult ESA-naГЇve anemic non-dialysis CKD patients. Treatment was 1624 weeks in six cohorts differing by starting dose (50-150 mg) and frequency
(QW, BIW, TIW) during Hb correction/maintenance. Dose titration was allowed
every 4 weeks to target Hb 11-13g/dL. Fe repletion at baseline (BL) was not
required and intravenous Fe was not allowed. Across cohorts, the diabetic
subjects were comparable in number (n=15-19/cohort) and BL traits, including
Hb (mean 9.7 g/dL; cohort range 9.6-9.9g/dL). Treatment to Hb targets resulted
in a mean peak Hb increase of 1.9 g/dL (cohort range 1.4- 2.3g/dL; p<0.0001)
and an 83-100% response rate, defined as Hb ≥11g/dL and ≥1g/dL from BL.
Across cohorts, there was a mean peak decrease from BL TC (170 mg/dL) of
Aims: To explore the effect of metformin and acarbose on islet О± cell function
in overweight and/or obese patients with newly diagnosed type 2 diabetes.
Materials and methods: Drug naГЇve patients with newly diagnosed type 2
diabetes, whose HbA1c between 6.3% and 9%, BMI greater than 24Kg/m2,
were enrolled. Patients were randomly assigned to metformin (1.5g/d) and
acarbose (100mg tid) group for a predictive follow-up period of 24 weeks.
Plasma glucose, insulin and glucagons at 0, 0.5h, and 2 h after the meal and
HbA1c were measured at baseline and 24 weeks.
Results: 108 patients, with the mean age of 51years, HbA1c 7.7%, BMI
26.8Kg/m2 were enrolled. 54 patients were assigned in metformin group,
the other in acarbose group. Baseline characteristics of both groups were
even. After 24-week treatment, glucose control improved significantly in both
metformin group and acarbose group (HbA1c:-1.24% and -1.28%; fasting
plasma glucose: 2.09 mmol/L and 1.53 mmol/L; 0.5h postprandial glucose:
2.27mmol/L and 2.87 mmol/L; 2h postprandial glucose: 3.19mmol/L and 3.25
mmol/L, respectively); The early-phase insulin secretion index О”I30/О”G30 was
improved only in acarbose group; Body weight decrease (metformin:-2.3Kg
vs. acarbose: -2.6Kg); Decrease of fasting and 0.5h postprandial glucagon in
For author disclosure information, see page LB66.
ADA-Funded Research
LB22
Clinical Diabetes/Therapeutics
15% (p<0.0001) (-25% in overall study). LDL changes were concordant in a
limited subset with available LDL samples. Mean BP was unchanged, with
a lower rate of hypertensive adverse events (AEs) (8%) than that reported
historically for ESAs. Overall, FG-4592 was well tolerated, with no drugrelated SAEs. In diabetic subjects with CKD, FG-4592 corrected/maintained
Hb without IV Fe and with a favorable cardiovascular risk profile. This suggests
a distinct pharmacological and clinical profile that may provide a safer and
more convenient therapy for treatment of CKD anemia. Phase 3 trials are in
progress.
and $29,331 per quality-adjusted life-year (QALY) gained from a health system
and societal perspective, respectively. In a hypothetical cohort without
diabetes, the ICER was $7,777 and $18,263 per QALY gained, respectively.
When excluding website-related costs (licensing, maintenance, and technical
support), the ODPP was cost-saving (health system) or cost $14,143 per QALY
gained (societal). Results were robust in sensitivity analyses, but enrolling
cohorts with lower annual risk of developing diabetes (<1.81%), enrolling
fewer participants (<16), or increasing the hourly cost (>$90) or the annual
per-participant time required (>1.44 hours) for ODPP technical support could
increase the ODPP ICER to be >$20,000 per QALY gained. In probabilistic
sensitivity analyses, the ODPP was cost-effective in 20-58% of model iterations
using an acceptability threshold of $20,000, 73-92% at $50,000, and 95-99%
at $100,000/QALY. The ODPP delivered in primary care settings for weight
management appears to be an economically reasonable intervention.
80-LB
Reversal of Suppressed Estrogen Receptor О± and Anti-Oxidant Levels:
Possible Benefits for Cardiovascular Disease (CVD) in Diabetic Kidney
Disease (DKD)
Supported by: USAMRAA (W81XWH-04-2-0030)
GARY E. STRIKER, ELENA M. YUBERO-SERRANO, SHOBHA SWAMY, SHARON J.
ELLIOT, WEIJING CAI, XUE CHEN, ELIZABETH MCKEE, ANITA KALAJ, FRIEDERIKE
KRUCKELMANN, LAUREN TIRRI, KAMALA MANTHA, ELIOT J. RAYFIELD, JAIME
URIBARRI, NIKOLAS HARBORD, RONALD TAMLER, GRISHMA PARIKH, AGUSTIN
BUSTA, LEONID PORETSKY, MARK WOODWARD, HELEN VLASSARA, New York,
NY, Miami, FL, Baltimore, MD
82-LB
Foot-In-Wallet Disease: Tripped Up by “Cost Saving” Reductions
GRANT H. SKREPNEK, JOSEPH L. MILLS, DAVID ARMSTRONG, Tucson, AZ
The purpose of this study was to assess changes in inpatient-related
outcomes associated with diabetic foot infections (DFIs) among adult
beneficiaries of Arizona Medicaid (Arizona Health Care Cost Containment
System, AHCCCS) following the 2009 announcement of reimbursement
coverage cancellation to podiatric physicians that was implemented in 2010
and intended to reduce costs (Arizona 49th Legislature, 7th Special Session;
SB1003, HB 2003). Inpatient discharge records from the Agency for Healthcare
Research and Quality Healthcare Cost and Utilization Project were used in
this retrospective cohort study spanning 2006-2010. Inclusion criteria involved
cases of all-listed diagnoses of inpatient DFIs among AHCCCS beneficiaries
≥18 years of age. An autoregressive integrated moving average (ARIMA)
interrupted time-series was used to estimate post-announcement changes
in outcomes of inpatient admissions, charges, length of stay, and severe
aggregate outcomes (SOAs) involving mortality, amputation, sepsis, or surgical
complications. Across the 5-year time period, 3,845 inpatient cases of DFI
among adult AHCCCS beneficiaries were observed, averaging 64.1 (В±20.4)
cases each month. Per case, the average length of stay was 7.0 (В±5.7) days and
mean charges were $54,046 (В±64,368), amounting to a total bill of $208 million
(USD 2012). SOAs occurred in 31.1% of cases. Following the announcement
of changes in AHCCCS podiatric service coverage, results of the interrupted
time-series analysis indicated 56.3% more admissions, 42.1% longer lengths
of stay, 52.1% higher state inpatient charges, and 86.1% more SAOs (p<0.001).
This evaluation of the cancellation of podiatric services within AHCCCS
suggests a marked worsening of patient care in terms of increased inpatient
admissions, lengths of stay, charges, and severe clinical outcomes. Restricting
access to preventive care among people with diabetes may manifest in serious
unintended consequences, particularly among the poor and underserved.
The expression/actions of estrogen receptor О± (ERО±) are reduced in postmenopausal females, high oxidative stress (OS) and inflammation (Infl) and
may underlie CVD risk in DKD. Advanced glycation endproducts (AGEs) cause
of increased OS/Infl in DKD. Sevelamer carbonate (SevCarb), blocks AGE
absorption from food, reduces OS and Infl, restores cellular anti-OS defenses
and improves glucose and lipids in DKD. We asked if SevCarb increases ERО±
expression in T2D. Subjects with HbA1c >6.5, eGFR 25-80ml/min/1.73m2, and
albumin excretion >300mg/day were randomized to SevCarb (4800mg/day) or
Ca2CO3 (1950mg/day) for 6 months in an intention-to-treat trial. At 3 months
there was a robust increase of ERО± levels and Nrf2 and AGER1 (markers of
anti-oxidant and anti-AGE defenses). Full-length RAGE, a pro-oxidant receptor
was reduced and there was a strong trend for reduction of TNFR1, a marker of
risk for CVD and progression of DKD.
Sevelamer Carbonate (n = 56) Calcium Carbonate (n = 50)
Mononuclear
Cell
ER О±
Nrf2
AGER1
TNFR1
RAGE
Mean
SD
1.503
0.497
0.284
-0.359
-0.100
3.515
1.662
1.001
1.841
0.765
p
value
0.003
0.025
0.035
0.144
0.086
Mean
SD
-0.358
-0.131
-0.045
0.331
0.419
0.941
0.991
0.446
1.491
1.413
p
p
value value*
0.011 0.003
0.350 0.009
0.532 0.028
0.168 0.052
0.059 0.011
*Statistical significance between deltas of both treatments (3 months minus
baseline).
In conclusion, ERО± restoration after sevelamer carbonate treatment may
underlie and reduced OS and inflammation and other anti-oxidant defenses in
DKD. It also decreased markers of progression in DKD and other risk factors
for CVD. A longer and larger clinical trial is necessary to determine if these
changes affect clinical outcomes.
The Cost of Diabetes: Escalating Trends and Cost Drivers
83-LB
NINA RAN, JESSICA DONG, MICHAEL DOUGAN, RICHARD KAHN, MARISSA H.
LYNN, LISA ROTENSTEIN, MARK YARCHOAN, KELLY CLOSE, San Francisco, CA,
Boston, MA, Chapel Hill, NC, Philadelphia, PA
Supported by: Sanofi
Diabetes-related costs place a significant burden on the US healthcare
system, accounting for 13% of total healthcare spending in 2012. The purpose
of this study was to analyze trends in costs and to determine which components
of diabetes care have made the greatest impact.
We analyzed published reports that used data derived from Federal
databases; one report with 2012 data was published only last month. The
cost of diagnosed diabetes in 2012 ($245 billion) continues to rise inexorably
from previous years: 2007--$174 billion; 2002--$132 billion; 1997--$98 billion;
and 1992--$92 billion. Costs have grown at a faster rate from a higher base,
rising 41% (27% inflation adjusted) from 2007 to 2012 compared to 32% (15%)
from 2002-2007, 35% (20%) from 1997-2002, and 7% (-7%) from 1992-1997.
Accounting for inflation and the number of diagnosed cases of diabetes,
annual total costs per capita has steadily decreased from $20,700 in 1992 to
$11,000 in 2012. Per capita institutional healthcare expenditure (i.e., inpatient
hospital days, nursing/residential care, hospice care) attributed to diabetes
has shown a parallel 54% decline from $8,880 in 1992 to $4,070 in 2012.
This has been partially offset by a steady increase in per capita costs for
outpatient care from $1,390 in 1992 to $3,820 in 2012; while a large absolute
increase, the per capita outpatient cost remains far less than that of inpatient
care. These data suggest a considerable reduction in the cost of expensive
diabetes complications that has been offset by improvements in outpatient
services. The cost of the latter consists mainly of medicines and supplies, as
well as provider-patient encounters. Thus, the greater and appropriate use of
Health Care Delivery—Economics
81-LB
Cost-Effectiveness of an Internet-Delivered Lifestyle Intervention in a
High Cardiovascular Risk Population in Southwestern Pennsylvania
SHIHCHEN KUO, JANICE C. ZGIBOR, KENNETH J. SMITH, KATHLEEN M.
MCTIGUE, RACHEL HESS, TINA BHARGAVA, CINDY L. BRYCE, Pittsburgh, PA,
Kent, OH
While Internet-delivered lifestyle interventions are effective for weight
control, their cost-effectiveness for diabetes prevention and risk reduction
in primary care settings is unclear. A Markov state-transition model was
developed to estimate the cost-effectiveness of using an Online adaptation
of the Diabetes Prevention Program lifestyle intervention (ODPP) compared
to usual care to reduce metabolic risk in an overweight/obese cohort (mean
age 53) over a 10-year time horizon. Intervention costs and weight change
outcomes were obtained from a prospective ODPP pilot study; other costs,
disease progression data, and utilities were drawn from published reports.
In the model, diabetes risk was a function of weight change with/without the
program. Compared to usual care, the base case incremental cost-effectiveness
ratio (ICER) of the ODPP in our pilot study cohort (30% diabetic) was $14,351
For author disclosure information, see page LB66.
ADA-Funded Research
LB23
Clinical Diabetes/Therapeutics
86-LB
medications and supplies has been of significant benefit. We conclude that
the cost of diabetes resides mainly in the growing number of those affected.
Continued, if not enhanced, attention to the delivery of quality outpatient
diabetes care will likely be the best approach to controlling costs, until efforts
to prevent diabetes become more widespread.
Optimal Glycemic Control Improves Clinical Outcomes in Patients
With Type 2 Diabetes
BORIS DRAZNIN, YUNJIAO WANG, STACEY A. SEGGELKE, MATTHEW HAWKINS,
JOANNA GIBBS, NEDA RASOULI, CECILIA L. WANG, Aurora, CO, Denver, CO
While the importance of glycemic control is well established for patients
with diabetes hospitalized for surgical problems, it has not been supported by
clinical studies for patients with diabetes hospitalized on the medical floors.
We conducted a retrospective study of 378 patients with Type 2 diabetes
admitted for cardiac or infectious disease (ID) diagnosis between Sep 1, 2011
and August 1, 2012. Exclusion criteria included Type 1 diabetes, admission
to the intensive care unit (ICU), hospital stay shorter than 3 days, and daily
glucocorticoid dose greater than 20 mg. The primary composite outcome
included death during hospitalization, ICU transfer, initiation of enteral or
parenteral nutrition, line infection, deep vein thrombosis, pulmonary embolism,
rise in plasma creatinine by 1 or over 2 mg/dl, new infection, an infection lasting
for more than 20 days, and re-admission within 30 days and between 1 and 10
months after discharge. Patients were stratified by mean blood glucose (BG)
level: Group 1 had mean BG of less than 180 mg/dl (n=286, mean BG 142В±23
mg/dl) while Group 2 had mean BG levels greater than 180 mg/dl (n=92, mean
BG 218В±34 mg/dl, p<0.0001). Group 2 had a 45% higher occurrence of the
primary outcome (p<0.0004). The rate of unfavorable events was greater in
cardiac and ID patients with worse glycemic control (Group 2). Consultation by
the inpatient Glucose Management Team (GMT) in Group 2 patients resulted
in a lower rate of composite outcome (p<0.03), less variability in blood glucose
levels (p<0.05), and an increase in the proportion of BG levels in the acceptable
glycemic range of 100-200 mg/dl (55В±12% in GMT-treated patients vs. 36В±15%
in non-GMT-treated patients; p<0.002). These data demonstrate that poor
glycemic control is associated with worse outcomes in hospitalized medical
patients with Type 2 diabetes. The involvement of a specialized GMT improves
outcomes in these patients by reducing glycemic variability and increasing the
proportion of BG values within an acceptable range.
84-LB
Resource Utilization and its Impact on the Inpatient Diabetes
Management in the Non-Critical Care Units
VIVEK BANSAL, NOORMUHAMMAD ABBASAKOOR, EUNICE Y. CHUANG,
TARANVEER K. PAWAR, OSAMA HAMDY, Boston, MA
With the growing number of admitted patients with diabetes and the
amplified hospitalization cost, it became quite important to explore the
best model of resource utilization for inpatient diabetes management. In
this double-blind study, we evaluated two models of care at an academic
center, one offered by primary service team (PST) vs. another by specialized
diabetes team (SDT). A total of 756 admissions to non-critical care units were
evaluated; 392 met eligibility criteria (type 2 DM for >3 months and nonpregnant). From them, 262 were matched in 1:1 ratio based on the mean of the
first four blood glucose values (4BG) with equal proportions from surgical unit
(45%). Baseline demographics for PST vs. SDT included: mean age 68.9В±11.0
vs. 59.0В±14.9 years (p=<.001), female gender 41.2 vs. 45.0% (p=0.5), mean 4BG
values 202.2В±52.5 vs. 203.1В±60.6 mg/dL (p=0.5), and mean of most recent A1C
7.3В±1.3 vs. 8.7В±2.1% (p=<.001). Overall 30-day readmission percentage was
22.1 with relative percentages of 21.4 in PST vs. 22.9 in SDT (p=0.089), and
rates of 30-day readmissions were 1.3В±0.5 vs. 1.1В±0.3 (PST vs. SDT, p=0.107).
Length of stay (LOS) was found to be significantly shorter for the PST group
(4.8В±1.9 vs. 5.3В±2.3 days, p=0.038). Surgical subgroup analysis showed shorter
LOS for PST (4.8В±1.9 vs. 5.6В±2.2 days, p=0.04), but the 30-day readmission was
20% with a frequency of 1.5 in PST and 1.1 in SDT (1.5В±0.7 vs. 1.1В±0.3 times,
p=0.026). No differences were seen in the medicine subgroup for all outcomes.
In interpreting these results, we should appreciate that the SDT cared for
sicker patients with higher A1C. This was also reflected in the observed wide
variability of BG levels during hospitalization. In conclusion: utilizing PST for
diabetes management in medical non-critical care unit is better resource
utilization and is advisable. Reserving SDT to only sicker patients with
higher A1C and for patients admitted to surgical non-critical care units may
significantly impact the 30-day readmission rate.
Pediatrics—Obesity and Type 2 Diabetes
87-LB
Validity of the 13C-Glucose Breath Test as a Screening Tool to Identify
Metabolic Syndrome in Mexican Pediatric Population
85-LB
ALEJANDRA SALAS-FERNГЃNDEZ, JORGE MALDONADO-HERNГЃNDEZ, AZUВ­
CENA MARTГЌNEZ-BASILA, GABRIEL MARTГЌNEZ RAZO, Distrito Federal, Mexico
Improved Real-World Glycemic Outcomes With Liraglutide versus
Other Incretin-Based Therapies in Type 2 Diabetes
Metabolic syndrome (MS) is an important risk factor in the pediatric
population for the early onset of type 2 diabetes mellitus and cardiovascular
disease. New non-invasive tools are required to identify MS in this population
to prevent chronic diseases in the future; the 13C-breath test shows different
advantages: simplicity, portability, sample stability and ease administration.
The aim of this cross-sectional study was to determine the validity of the
13C-glucose breath test to identify MS in Mexican pediatric population.
Children between 10 and 16 years old were recruited and divided in two
groups: the control group (n=31) included subjects without any component of
MS and the MS group (n=33) consisted of subjects with MS according to the
modified criteria proposed by the International Diabetes Federation in pediatric
population. A blood sample was taken to determine glucose, triglycerides and
HDL-cholesterol concentrations. The waist circumference and blood pressure
were determined. After the ingestion of 1.75 g/Kg of glucose and 1.5 mg of
universally labeled 13C-glucose/Kg dissolved in water, breath samples were
taken at baseline, 30, 60, 90, 120, 150 and 180 minutes.
The cumulative percentage of oxidized dose of 13C-glucose was significantly
different (p<0.05) between the study groups at the times previously described,
however the greatest difference was found at 180 minutes (17.75% В± 5.64 in
control group and 9.95% В± 4.73 in MS group).
A ROC curve was constructed obtaining a cutoff point of 14.45 of cumulative
percentage of oxidized dose of 13C-glucose at 180 minutes which corresponded
to a sensitivity of 82% and specificity of 84% (AUC: 0.87, p<0.001, CI95:0.780.95).
The results obtained demonstrate that the 13C-glucose breath test is a
valid screening method to identify MS in Mexican pediatric population and
represents an alternative in non-clinical settings where venipuncture and
blood retrieval results impractical or impossible.
MITCHELL DEKOVEN, WON CHAN LEE, JONATHAN R. BOUCHARD, MARJAN
EDWY, JAKOB LANGER, Alexandria, VA, Princeton, NJ
Outcomes on A1c in clinical practice were retrospectively compared among
patients ≥18 years with type 2 diabetes (T2D) who initiated liraglutide (LIRA),
exenatide (EXEN) or sitagliptin (SITA), including sitagliptin/metformin, using
the IMS integrated data warehouse. Patients were required to be GLP-1-and
DPP-4-naïve during a 6 month pre-index period, with ≥1 prescription for LIRA,
EXEN or SITA between January 2010 and December 2011 (index period). Only
patients who were persistent on their index treatment (LIRA, EXEN or SITA)
regimens for 180 days post-index were included in the analysis. Patients who
were pregnant or used insulin in the pre- or post-index periods were excluded.
Changes in A1c from baseline (45 days pre-index through 7 days post-index) to
follow-up (180 days post-index [В±45]), and the proportion of patients reaching
A1c<7%, were examined using multivariable regression methods to adjust
for confounding factors such as age, gender, region, comorbidities, baseline
A1c and background antidiabetic treatment. At follow-up, changes in A1c
(%-point) and the proportion of patients achieving A1c<7% were significantly
greater with LIRA compared with EXEN and SITA (Table). These real-world
data suggest that initiating LIRA was associated with significantly greater
reductions in A1c and improved glycemic goal attainment than EXEN and SITA
among patients with T2D.
LIRA EXEN SITA
Sample size
234
182
1,757
p
p
Baseline A1c
7.8% 7.8% 7.9% (LIRA-EXEN) (LIRA-SITA)
Change in A1c from baseline -1.08% -0.75% -0.68% P<0.001 P<0.0001
Pct. achieving A1c<7%
64% 54%
49%
P<0.05 P<0.0001
Supported by: CONACYT
Supported by: Novo Nordisk, Inc.
For author disclosure information, see page LB66.
ADA-Funded Research
LB24
Clinical Diabetes/Therapeutics
88-LB
90-LB
A Community-Based Intervention for Diabetes Risk Reduction in InnerCity Obese Adolescents
Metabolites as Novel Biomarkers for Childhood Obesity-Related Traits
in Mexican American Children
MARY SAVOYE, SONIA CAPRIO, JAMES DZIURA, ANNE CAMP, FANGYONG LI,
MELISSA SHAW, GRACE KIM, WILLIAM V. TAMBORLANE, New Haven, CT
VIDYA S. FAROOK, LAVANYA REDDIVARI, GEETHA CHITTOOR, SOBHA PUPPALA,
RECTOR ARYA, SHARON P. FOWLER, BIRUNDA MOHAN, KELLY J. HUNT, JOANNE
E. CURRAN, ANTHONY G. COMUZZIE, DONNA M. LEHMAN, CHRISTOPHER P.
JENKINSON, JANE L. LYNCH, RALPH A. DEFRONZO, JOHN BLANGERO, DANIEL
E. HALE, RAVINDRANATH DUGGIRALA, JAIRAM VANAMALA, San Antonio, TX,
Fort Collins, CO, Charleston, SC
Childhood obesity has been accompanied by an increasing prevalence of
type 2 diabetes (T2D), particularly in minority children. 20-30% of obese youth
have “pre-diabetes” a precursor to diabetes marked by insulin resistance,
ОІ-cell dysfunction and impaired glucose tolerance (IGT). The Diabetes
Prevention Program demonstrated T2D could be prevented/delayed by lifestyle
modification in adults with pre-diabetes, but efficacy of similar interventions
in youth has not been established. Therefore, we evaluated the effects of
the Bright Bodies (BB) Healthy Lifestyle Program on 2-hr OGTT glucose in
comparison to children receiving standard of care with a parallel-group
randomized controlled trial comparing BB with standard clinical care (CC) in
obese adolescents (10-16 yo) with elevated OGTT 2-hr blood glucose (130-199
mg/dl) from an ethnically-diverse population.
OGTTs, including anthropometric and metabolic syndrome assessments,
were conducted at baseline and 6 mos. Children attended BB twice weekly
for exercise and nutrition/behavior modification and CC group received clinical
care from their pediatrician. Primary outcome was change in 2-hr OGTT glucose
and % conversion from elevated 2-hr blood glucose to non-elevated (<130 mg/
dl) 2-hr blood glucose. Changes in outcomes were compared between groups
using a mixed model with covariate adjustment for baseline outcome and
multiple imputation for missing data. Least squares means and 95% CIs were
estimated for changes in outcomes.
Reductions in 2-hr glucose were more favorable in BB compared to CC (-27.2
vs. -10.1 mg/dl; diff=-17.1, 95% CI ;p= 0.005). Moreover, greater conversion
to <130 mg/dl 2-hr glucose occurred in BB than CC (p=0.03). Other insulin
sensitivity indices were significantly improved, as well as the prevalence of
metabolic syndrome in the BB group (p=0.004).
Compared to standard of care, the Bright Bodies Program is a more effective
means of reducing the risk of T2D in obese adolescents with elevated 2-hr
blood glucoses.
Childhood obesity has become a major public health issue and has spurred
continued efforts to understand the mechanisms influencing it. Although newer
approaches have identified several metabolites associated with obesity, there
is a paucity of such studies in ethnic minorities including Mexican American
(MA) children. We therefore, attempted to identify systemic metabolites,
reflective of metabolic processes, associated with obesity by performing
global serum metabolite screening in 14 obese, 13 overweight and 15 normal
MA children (6-17 years), using the UPLC system with Micromass Q-Tof Micro
mass spectrometer. Among the ~850 metabolites detected, we identified 14
metabolites with significant (P≤0.018) differences between obese and normal
weight children by ANOVA. Higher levels of bradykinin, phosphocholine and
phosphotidylethanolamine and lower levels of L-thyronine, naringenin, indole3-propionic acid, 2-methylbutyroylcarnitine, 3-hydroxyquinine, 1О±,22-dihydroxy23,24,25,26,27-pentanorvitamin D3, lysophosphatidylcholine (18:1), calciferol
B, diglyceride, malvidin3-(6-acetyl glucoside) and linoleic acid were found in
obese children. After adjustment for multiple testing (significance threshold
= P<5.9x10-5), L-thyronine (18.2 fold); bradykinin (4.2 fold); and naringenin
(1.8 fold) remained significant. We examined associations between these
metabolites and 6 cardio-metabolic traits: waist circumference (WC), systolic
blood pressure (SBP), diastolic blood pressure (DBP), HOMA-IR, triglyceride
(TG), and HDL-cholesterol (HDL-C) using SOLAR. Interestingly, except for
2-methylbutyroylcarnitine, all the metabolites were significantly (P≤0.05)
associated with one or more of the obesity-related traits. For example,
L-thyronine was negatively correlated with WC, SBP, DBP, HOMA-IR, TG and
positively correlated with HDL-C. To our knowledge, this is the first study,
albeit pilot to identify these novel biomarkers of childhood obesity.
Supported by: NCRR; NIH
89-LB
Pediatrics—Type 1 Diabetes
Even If Not Macrosomic, Children of Diabetic Mothers Tend to be
Overweight at Age 17
91-LB
ZVI LARON, ALON FARFEL, RONA RABINOVITZ, TAMAR LARON-KENET, MOSHE
HOD, RONY CHEN, GADI KAMPINO, DORIT TZUR, ESTELLA DERAZNE, Petah
Tikva, Israel, Tel Aviv, Israel
Performance of a New CGM System in Youths With Diabetes:
Comparisons With SMBG and YSI
We have shown previously that newborns born long and/or overweight tend
to be tall and obese at age 17, however data on adult height and weight of
children born to diabetic mothers is scant. We studied all full term neonates of
diabetic mothers born between 1987 and1993 in the Rabin Medical Center in
Israel. The control group consists of neonates born to healthy mothers during
the same period. The birth length and weight and height, weight and BMI at
age 17 as measured at the recruitment centers of IDF, were compared between
groups. There were 447 children (235 males) from mothers with gestational
diabetes (GDM), 97 children (51 males) from mothers with pre-gestational
diabetes (PGDM) and 544 children (265 males) in the control group. At age
17 we were able to track 674 adolescents (61.95% of the original groups).
The main findings are shown in the Table. There was no significant difference
in birth length or weight between the groups. Our study shows that improved
treatment of diabetes during pregnancy in the 1990’s resulted in normally
sized newborns. Nevertheless, children born to diabetic mothers tend to be
overweight adolescents and are at risk to develop future metabolic syndrome.
Males
Males
Males
Males
Females
Females
Females
Females
Number
GDM 159 PGDM 34
Birth length
49.7В±2.0 49.3В±1.8
Birth weight
3423В±527 3451В±535
BMI≥85th
percentile at age 17
27.0%
26.5%
Number
113
23
Birth length
48.7В±2.0 48.6В±1.7
Birth weight
3230В±510 3210В±364
BMI≥85th percentile at age 17 15.9%
34.8%
LORI M. LAFFEL, BRUCE BUCKINGHAM, DAVID PRICE, KATHERINE NAKAMURA,
TIMOTHY S. BAILEY, MARK DANIELS, DAVID R. LILJENQUIST, PETER CHASE,
Boston, MA, Stanford, CA, San Diego, CA, Escondido, CA, Chino, CA, Idaho Falls,
ID, Denver, CO
We studied the performance of the new Dexcom G4 PLATINUM (DG4P)
CGM system in 176 youth (age 2 - 17, mean 11.5,29 < age 6; 57% male),
at 6 centers. Most youth (72%) used CSII; mean A1C was 8.2 В± 1.3%; and
mean zBMI was 0.5 (range -4.7 to 2.6). Youth wore 2 systems (1 blinded, 1
displayed) on either the abdomen and/or upper buttocks for 7 days of home
use. Youth/parents calibrated CGM twice daily using fingerstick SMBG . There
was a single in-clinic session on sensor days 1, 4, or 7. In youth ≥ 6 years,
the session lasted up to 6 hrs in which “arterialized” (via a heating pad over
an arm IV) venous YSI samples q15 mins and SMBG samples q30 mins were
collected. In youth <6 years, there was only SMBG samples q30 mins collected
for up to 4 hrs. Compared to SMBG, the DG4P MARD was 15% (n= 16318),
14% on the abdomen, and 16% on the buttocks. Accuracy was similar when
supplemental topical adhesives to secure the sensor or during different time
of the day. The MARD was 17% in ages 2-5, 16% in ages 6-12, and 15% in
ages 13-17. The MARD of the sensor decreased from 19% on day 1 to 12%
on day 7. In a comparison of SMBG to YSI, MARD was 13% (n= 1296), higher
than expected. As a result, the DG4P MARD using YSI reference was 17%
(n=2922). After adjustment for the bias of venous and capillary glucose values
in simulated post-hoc analyses, the MARD of CGM to YSI reduced to 15%,
similar to the SMBG reference. The precision analysis showed a CV of 7%
overall, 6% on the abdomen, and 7% on the buttocks. 85% of sensors lasted
7 days and 95% of possible data displayed on the receiver. There were no
serious or unanticipated device events, sensor fractures, or infections. This is
largest pediatric CGM performance study to date, and included young children
2-5. DG4P performance compared favorably to the CGM system currently
approved for pediatric use. There were minor differences at wear sites and
across age groups. Performance of SMBG and CGM in comparison to YSI was
likely impacted by arterialization challenges in youth. After adjustment, the
DG4P performance to YSI was similar to SMBG.
Control 198 P
49.6В±1.6 0.37
3344В±372 0.18
16.1% 0.009*
147
48.9В± 1.9 0.610
3228В±324 0.978
15.6%
0.441*
* p<0.05 between the control group and the 2 other groups combined
For author disclosure information, see page LB66.
ADA-Funded Research
LB25
Clinical Diabetes/Therapeutics
92-LB
94-LB
The Impact of Diabetic Ketoacidosis (DKA) History on Brain
Microstructural White Matter (WM) and Memory Function in Young
Children With Type 1 Diabetes (T1D)
Identify High Risk for Type 1 Diabetes: ECL-GADA and IAA Assays
LIPING YU, DONGMEI MIAO, KATHERINE M. GUYER, LING JIANG, FRAN DONG,
ANDREA K. STECK, MARIAN J. REWERS, Aurora, CO
Detection of diabetes-specific islet autoantibodies is essential for prediction
and prevention of type 1 diabetes. The present study aimed to identify high risk
for typ1 diabetes with newly developed more specific assays for insulin and
GAD65 autoantibodies. In addition to a previously reported non-radioactive
electrochemiluminescense-based ECL-IAA assay, we recently developed
an ECL-GADA assay. The assays were validated using serum samples
from 227 newly diagnosed diabetic children, 68 pre-diabetic children who
were prospectively followed to type 1 diabetes, 130 non-diabetic children
longitudinally followed for years with confirmed islet autoantibodies to insulin,
GAD65, IA2 and/or ZnT8, and 181 age-matched healthy antibody negative
children. Both ECL-GADA and ECL-IAA were able to pick up 100% of antibody
positivity detectable with current radioassay among newly diagnosed children
with type 1 diabetes, pre-diabetic children, and high risk children with multiple
positive islet autoantibodies. On the other hand, only a small portion of
children positive for a single islet autoantibody by radioassay were positive for
either ECL-GADA (9/39 [23%]; p<0.0001) or ECL-IAA (13/35 [37%]; p< 0.0001).
Both IAA and GADA not detectable by ECL assay were shown to be of low
affinity. In conclusion, new ECL-based assays for IAA and GADA were more
disease specific and may help to differentiate high-risk from low-risk single
islet autoantibodies for staging of type 1 diabetes.
TANDY AYE, ALLISON CATO, NAAMA BARNEA-GORALY, PEIYAO CHENG, CRAIG
KOLLMAN, KATRINA RUEDY, ROY BECK, NELLY MAURAS, ALLAN REISS, BRUCE
BUCKINGHAM, STUART WEINZIMER, EVA TSALIKIAN, LUCY LEVANDOSKI,
TAMARA HERSHEY, Stanford, CA, Jacksonville, FL, Tampa, FL, New Haven, CT,
Iowa City, IA, St. Louis, MO
Children with T1D are at risk of developing neurocognitive complications
but the extent and mechanisms of these remain unknown. Subtle learning and
emotional problems and poor concentration have been reported in children
following an episode of DKA and evidence suggests long-lasting decreases in
memory function in school-aged children years after a DKA
episode. To determine if a history of DKA was associated with memory and
brain changes in young children (ages 4 to 10 years) with T1D, we analyzed
data from a DirecNet study assessing neuroimaging and cognitive differences
in children in this age range. One hundred forty-two children with T1D
completed subtests of the Children’s Memory Scale and unsedated diffusion
weighted MRI scans. There were 51 episodes of DKA, 46 at diagnosis of DKA,
in 51 subjects. The median time from the DKA event to cognitive testing was
3.1 years (range 0.1 to 7.6 years). After controlling for age of onset and sex,
a history of DKA was not related to memory scores. However, increasing
clinical severity of DKA (mild=pH<7.3 or C02<15; moderate=pH<7.2 or C02<10;
or severe=pH<7.1 or C02<5) was significantly correlated with higher radial
diffusivity (RD) and lower fractional anisotropy (FA) (p<0.05, corrected) in
widespread brain regions. In addition, more severe DKA was associated with
higher axial diffusivity (AD) (p=0.05, corrected) in the right frontal, temporal
and parietal brain regions. Longitudinal studies of these children may predict
memory deficits seen later in older children. These data indicate that even a
single episode of moderate to severe DKA in very young children with T1D can
have long-term effects on brain white matter microstructure.
Supported by: NICHD
93-LB
Ultrasensitive Measurement of C-Peptide in Serum and Urine Using
Novel Electrochemiluminescent Technology
STEVE B. PHAGOO, JEANNE M. SLOAN, KELLY Y. CHUN, Calabasas Hills, CA
C-peptide is a 31-aa protein that connects insulins’ A-chain to its B-chain
in the proinsulin molecule. The measurement of C-peptide in serum and urine
are used to assess insulin secretory reserve levels, impaired glucose tolerance
and insulin resistance.
We have developed an ultrasensitive two-site C-peptide immunoassay using
electrochemiluminescent (ECL) detection technology (Meso Scale DiscoveryВ®,
MSD). The assay is capable of measuring C-peptide down to 0.004 ng/mL in
human serum and urine and is designed as a two-step reaction utilizing a pair of
monoclonal antibodies raised against human C-peptide. One of the antibodies
(capture) is immobilized on the carbon surface of the MSD 96-well plate while
the other antibody is conjugated with an ECL signal (MSD Sulfo tagв„ў) molecule
to generate a signal antibody. C-peptide samples are allowed to react in the
capture antibody coated plate, then incubated with the signal antibody. Bound
complex emits light upon application of electrochemical stimulation initiated
at the electrode surfaces of the microplate.
The wide dynamic range ECL technology allowed an assay range of 0.004
ng/mL to 8 ng/mL. The lower limit of quantitation (inter-assay CV 20.4% and
bias 2.3%) was 0.004 ng/mL. Inter-assay CV for serum samples at 1.5, 2.7
and 4.8 ng/mL was 5.0%, 3.2% and 6.9% respectively. Dilutional linearity
of high C-peptide serum samples provided mean recoveries of 101% and
110%. Recovery in serum was within +15% in the presence of high levels of
bilirubin, Intralipid or hemoglobin and there was little or no effect on C-peptide
in the presence of spiked normal physiological levels of proinsulin or insulin.
C-peptide in serum and urine were stable at ambient temperature for one day,
refrigerated or frozen temperature for up to 7 days, and up to six freeze/thaw
cycles.
The C-peptide serum and urine ECL method combines novel technology with
high assay performance and exceptional sensitivity that may exceed most
commercial diagnostic C-peptide assays.
The Effect of Type I Diabetes Mellitus on Final Adult Height
95-LB
ZARANA BAYONA, ROBERT J. TANENBERG, JENNIFER A. SUTTER, QIANG WU,
Greenville, NC
Studies have shown that Type I diabetes (T1DM) can impair linear growth
in children due to its effect on the insulin like growth factor 1 (IGF-1) system.
Patients with T1DM seen in the pediatric endocrinology clinic at ECU between
the ages of 8 and 18 years were included in a retrospective chart review.
Parental heights were obtained and gender adjusted mid-parental heights were
calculated using the formula described by Tanner. Each patient’s final adult height
was the height at age 18 if growth velocity in the preceding 6 months was zero.
Final adult height was subtracted from the predicted height to determine the
height difference (predicted minus final). Height difference was compared to the
subject’s average hemoglobin A1C (A1C) values from age of onset to 18. The data
was analyzed by linear regression of height difference on A1C.
We conducted a survey of adolescents in the pediatric diabetes clinic to
assess their knowledge of impaired growth as a complication of uncontrolled
T1DM and if this knowledge would motivate them for better diabetes control.
Twenty-seven patients with T1DM were included (18 males, 9 females). The
average A1C for all patients was 9.2% (S = 1.1) and average height difference
was 2.1 inches (S = 2.3). Only three patients showed a gain in height from the
predicted height and all had an A1C less than 9%. The regression analysis of
height difference on A1C had an r-squared = 0.06 and correlation of r = 0.25 (P
= 0.21). Data from 111 surveys showed that on a scale of 1 to 10 (least to most
important), average score for importance of final adult height was 7.3 for males
and 6.3 for females. Ninety-one percent of adolescents surveyed believed they
would work harder on their diabetes control if the complication of impaired
growth was known.
Although our results were not statistically significant, the scatter plot of A1C
to height difference shows a striking trend. For every 1% increase in the A1C,
children are predicted to lose about one-half inch from predicted height (slope
B= 0.51, S = 0.4, CI = -0.31-1.34).
For author disclosure information, see page LB66.
ADA-Funded Research
LB26
Epidemiology/Genetics
Pregnancy—Basic Science
retrospective cohort study of women who underwent screening and diagnostic
testing for GDM. Women with preexisting diabetes were excluded. Subjects
were divided into non-overlapping groups: GDM by CC, IADPSG GDM criteria
but not CC, and normal GDM screening/testing (control). Outcomes included
newborn birth weight (BW), BW z-score, ponderal index (PI) and percent
>90%ile for gestational age (%LGA). Data was analyzed with one-way ANOVA
with Tahmane method for multiple comparisons, t-tests, or Chi-squares. 8390
women were identified with 338 CC; 271 IADPSG; and 7771 controls. Maternal
characteristics including age (29.0 vs. 28.5 vs. 25.0 yrs, p<0.01), BMI (35.9 vs.
35.6 vs. 32.3 kg/m2, p<0.01) and race (Caucasian 41.1% vs. 47.0% vs. 36.4%,
p<0.01) differed among the groups. Mean BW (3411 vs. 3240g, p<0.01), BW
z-score (0.477 vs. 0.059, p<0.01), PI (2.79 vs. 2.73 g/cm3, p=0.014), and %LGA
(19.9 vs. 8.8%, p<0.01) were higher in IADPSG vs. controls with no difference
in gestational age at delivery (39.1 vs. 39.3 wks, p=0.08). Compared to CC
neonates, IADPSG had greater BW (3288 vs. 3411g, p<0.01) and gestational
age at delivery (38.6 vs. 39.1 wks, p<0.01) with no difference in %LGA (16.0
vs. 19.9%, p=0.20) or BW z-score (0.330 vs. 0.477, p=0.06). Women who would
be diagnosed as GDM by IADPSG criteria have newborns with greater BW,
BW z-score and %LGA compared to women with normal glucose testing. No
significant difference was found in BW z-score or %LGA between GDM by CC
criteria or IADPSG.These data support a recommendation to consider including
women with IADPSG criteria as GDM assuming that treatment improves
outcome.
96-LB
Circulating Markers of Endothelial Dysfunction and Glutathione
Peroxidase Activity in Normal Pregnancy
XINHUA CHEN, THERESA O. SCHOLL, Stratford, NJ
Endothelial dysfunction is positively related to insulin resistance and
cardiovascular disease. Oxidative stress increases and antioxidant status
decreases expression of endothelial adhesion molecules. We examined the
relationship between markers of endothelial dysfunction and glutathione
peroxidase activity, an indicator of antioxidant status, in normal pregnancy.
Pregnant women (N=230) were randomly selected from a prospective cohort
of normotensive, non-diabetic gravidae (African-American 35%, Hispanic 46%,
Caucasian 19%) age 21.7В±0.2 (yr), pregravid BMI (kg/m2) 25.2В±0.3. Serum
levels of soluble intercellular and vascular cell adhesion molecules (sICAM-1,
sVCAM-1 and E-selectin) and glutathione peroxidase (GPx) were measured at
entry to care (week 16) and the 3rd trimester (week 30). Data were analyzed
by multiple regression analysis controlling for age, BMI, smoking, parity and
ethnicity. At entry, significant negative associations were observed between
GPx activity and endothelial dysfunction markers including sICAM-1 (-1.896
ng/ml per mU/mg hemoglobin (Hb) GPx, p=0.009), sVCAM-1 (-2.687 ng/ml per
mU/mg Hb GPx, p=0.026) and sE-selectin (-0.348 ng/ml per mU/mg Hb GPx,
p=0.006). The relationship persisted at the 3rd trimester for sICAM-1 (-2.011
ng/ml per mU/ mg Hb GPx, p=0.027) and sE-selectin (-0.460 ng/ml per mU/mg
Hb GPx, p=0.007) but not sVCAM-1 (-0.970 ng/ml per mU/mg Hb GPx, p>0.05).
In conclusion, the inverse associations between maternal circulating
soluble adhesion molecules and GPx activity suggest a link between
endothelial dysfunction and antioxidant defenses. Increasing antioxidant
status may modulate circulating levels of soluble adhesion molecules and
prevent endothelial damage, thus reducing susceptibility to the pregnancy
complications like preeclampsia or gestational diabetes mellitus.
99-LB
Self-Report and Medical Record Agreement of Pregnancy Outcomes
in Women With Diabetes
ANDREA RODGERS FISCHL, SUSAN SEREIKA, WILLIAM HERMAN, DOROTHY
J. BECKER, PATRICIA SCHMITT, BLAIR POWELL, ANA DIAZ, JEFI JAUSTINE
BUENAVENTURA, JESSICA CHOI, MONICA CISTRONE, KAITLIN MALONE, ABBEY
PARROTT, DENISE CHARRON-PROCHOWNIK, Pittsburgh, PA, Ann Arbor, MI
Previous studies have shown that self-report may not be as accurate
as medical records. The purpose of this analysis was to investigate the
agreement between self-report (SR) and medical record (MR) documentation
of pregnancy outcomes, e.g., length of hospitalization, infant birth weight, and
maternal and fetal complications in women with T1D. An online SR follow-up
survey to evaluate long-term reproductive health outcomes is being conducted
with women who participated in a preconception counseling (PC) randomized
control trial (READY-Girls) as an adolescent with a matched comparative group
of women with T1D who did not receive PC as teens. Pregnancy outcomes
are also being collected from MR. Agreement was assessed using kappa
and intra-class correlation (ICC) coefficients. Ninety-one women (49 RCT, 42
matched) were recruited (age range 18-35yrs). Twelve (13.2%) of these women
reported 28 pregnancies. These 12 had a mean age of 27.5 (+4.2) yrs., 100%
were Caucasian, 25% had some college, and a mean duration of diabetes
= 20.3 (+7.1) yrs. Perfect agreement (kappa=1.0) was observed between SR
and MR for type of delivery, live birth, and infant birth weight >9lbs. Excellent
agreement was observed for baby’s actual weight (ICC=.943; mother’s selfreport was on an average 0.31 lbs lower than MR). Lower levels of agreement
were found in duration of hospitalization [mothers reporting longer stays
for themselves (ICC=.429) and their babies (ICC=.459)]. There is excellent
agreement between the self-report and medical record data for several of the
pregnancy outcomes in these participants with T1D. Self-report of pregnancy
outcomes should be verified by medical record data for infant birth weight and
length of hospitalization, suggesting that reporting of these types of variables
may not be interchangeable. Time between delivery and self-report may
influence mother’s recall and should be included in multivariate analyses.
Supported by: NIH
97-LB
ACE C1237T Gene Polymorphism in Indian Women With Gestational
Diabetes Mellitus
PARUL AGGARWAL, KRISHNA DALAL, NUTAN AGARWAL, NIBHRITI DAS, SUMIT
SHARMA, New Delhi, India, Linkoping, Sweden
Polymorphisms in the Angiotensin Converting Enzyme (ACE) gene in
patients with Type 2 diabetes have been reported to have contradicting results
in different populations. A report studying ACE Insertion/Deletion (ACE I/D)
in the intron16 of ACE gene with respect to Gestational Diabetes Mellitus
(GDM) in Czechoslovakian women found no association. Villard et al reported
several polymorphisms in the ACE gene, among which was a polymorphism
ACE 6(ACE C1237T) in exon 8. Two previous studies involving (Keavney et al
in 1998 and Zhu et al 2000) ACE-6 polymorphism and hypertension focused
on haplotyping only. The current study is the first to evaluate the role of ACE
6 polymorphism in women with GDM. Our study determined the occurrence
of genotype and allele frequencies of ACE 6 polymorphism in a genetically
homogeneous population. We enrolled 215 Indian women, comprising of
115 healthy pregnant women (control group) and 100 pregnant patients with
clinical diagnoses of GDM (study group). The ACE 6 alleles were visualized
by assays based on polymerase chain reaction and restriction endonuclease
analysis. The ACE C1237T polymorphism showed a strong association with
GDM (П‡2 = 5.50, p=0.0190). Further analysis revealed that the ACE T/T 1237
genotype was positively associated (95 % CI=0.1135-0.9281, OR= 0.34) with
GDM. This is the first study reporting association of the ACE 6 polymorphism
with GDM, probably indicating that ACE 6 gene can be considered as one of
the genetic marker for GDM.
Epidemiology—Aging
Supported by: AIIMS (to K.D.)
Pregnancy—Clinical
The Aging Islet of Langerhans
100-LB
JOANA ALMACA, JUDITH T. MOLINA, PER-OLOF BERGGREN, ALEJANDRO
CAICEDO, HONG GIL NAM, Miami, FL, Daegu, Republic of Korea
98-LB
The incidence of T2D increases dramatically with age. Because it is
unclear how islet-specific factors as opposed to systemic factors (e.g. insulin
resistance, vascular senescence) contribute to aging of the islet, we aimed
at identifying the intrinsic mechanisms responsible for age-related changes
in islet physiology. We compared islets from old (18-months, “old islets”)
and young mice (2-months, “young islets”) and examined their function
and structure longitudinally in vivo, in vitro, and after transplantation into
young mice. Although glucose tolerance did not change with age, old mice
were insulin resistant and had higher plasma insulin concentration under
fed conditions. Old islets were larger than young islets but exhibited similar
For author disclosure information, see page LB66.
Delivery Outcomes in Infants of Women Who Would Be Added to the
Diagnosis of Gestational Diabetes by IADPSG Criteria
JOHN K. ETHRIDGE, THADDEUS P. WATERS, PATRICK M. CATALANO, Cleveland,
OH, Chicago, IL
Based on the NIH consensus conference regarding gestational diabetes
(GDM), it is unclear if women who meet IADPSG criteria should be included
as GDM. Therefore, we sought to assess perinatal outcomes with Carpenter/
Coustan (CC) criteria for GDM, those with normal glucose testing, and those
who would be added to the diagnosis of GDM by IADPSG criteria. This is a
ADA-Funded Research
LB27
Epidemiology/Genetics
vascular density, capillary diameter and pericyte coverage. In old islets,
however, blood vessels expressed the inflammatory markers ICAM-1 and
VCAM-1 and the density of macrophages increased. These results suggest that
old islets are able to adapt to increased insulin demand, but this is associated
with local inflammation. To isolate islets from the systemic influences of the
aging organism we transplanted old and young islets into the eye of young
diabetic animals. Young islets readily engrafted and reversed diabetes. By
contrast, old islets showed poor engraftment, as evidenced by defective
revascularization with disproportionately large blood vessels, and a 30d delay
to return to normoglycemia. Three months after transplant, recipients of old
islets were normoglycemic but were glucose intolerant and had significantly
lower plasma insulin. However, glucose metabolism in these animals gradually
became better concomitantly with an increased incidence of blood vessels
with smaller diameter in old islet grafts. Our results suggest that old islets
transfer their inflamed vascular phenotype that delays engraftment and
revascularization but, as the islet recipient continues to gain weight, old (and
young) islet grafts grow, and increasingly display a normal microvasculature to
become fully functional.
p< 0.001). The area under the receiver operating characteristic curve (AUC)
for detecting undiagnosed diabetes was 0.75 for total population, 0.74 for
men and 0.78 for women (p=0.04); 0.76 for White, 0.76 for Black and 0.72 for
Hispanics (p=0.03 for White vs. Hispanics). The AUC for detecting pre-diabetes
was 0.67 for total population, 0.66 for men and 0.70 for women (p< 0.001);
0.68 for White, 0.67 for Black and 0.65 for Hispanics (p<0.001 for White vs.
Hispanics). The optimal cutoff point for detecting undiagnosed diabetes was
9 (sensitivity=0.83) for men and 10 (sensitivity=0.88) for women. The optimal
cutoff point for detecting pre-diabetes is 8 (sensitivity=0.68) for men and 9
(sensitivity=0.76) for women. In summary, findings from this study suggest
that the FINDRISC can be used as a simple and non-invasive screening tool
to identify individuals at high risk for diabetes in the U.S. adult population. In
this evaluation, the FINDRISC performed better in women than in men, in nonHispanic White than in Hispanics.
103-LB
Association of White Blood Cells Types With Incident Type 2 Diabetes:
The Insulin Resistance Atherosclerosis Study
Supported by: DGIST (Republic of Korea)
CARLOS LORENZO, ANTHONY J. HANLEY, STEVEN M. HAFFNER, San Antonio,
TX, Toronto, ON, Canada
The relation between white blood cell (WBC) type and development
of diabetes has received scant attention. Neutrophil count may reflect
inflammation. Therefore, we hypothesized significant diabetic risk associated
to this WBC type. We examined this issue in 866 participants who were
non-diabetic at baseline. Incident diabetes was ascertained after a 5.2-year
follow-up using the 2003 ADA diagnostic criteria. Insulin sensitivity index (SI)
was directly measured. All three WBC types were related to metabolic traits
with neutrophil and lymphocyte counts being more strongly associated with
inflammation and adiposity, respectively.
Epidemiology—Cardiovascular Disease
101-LB
Pain Qualities and STEMI: The Croatian Experience: Can Type 2
Diabetics Benefit from Silent Myocardial Ischemia Screening?
Л‡
Л‡
MARINA GRADIЕ ER, EDGAR GLAVAЕ , JASNA CMRECNJAK,
BRANKO OSTRICKI,
Вґ C,
Вґ MILJENKA IGREC, DAVOR MILICI
Л‡ C,
Вґ MAЕ A
GORAN TOPLEK, KORANA CURI
Вґ Cakovec,
Л‡
KATIC,
Croatia, Zagreb, Croatia
Coronary artery disease (CAD) is one of the leading causes of morbidity and
mortality in patients with type 2 diabetes mellitus (DM). The aim of our study
was to determine whether diabetic STEMI patients arrive in the Emergency
room (ER) later than nondiabetics, compare the differences in pain quality and
quantity between these groups, and measure differences in the outcome of
the index hospitalization. We expected impaired pain perception and atypical
symptoms to cause diabetic patients to seek out medical help later than
nondiabetics, and subsequently have worse outcome. A total of 266 patients
with first STEMI were included in our study during 2 years, 62 were diabetic
and 204 were nondiabetics. Pain intensity and qualities at admission were
measured using a modified McGill short form questionnaire. Other data was
collected from hospital electronic records. Diabetic patients did not arrive
significantly later than nondiabetics; 56% arrived within 120 minutes of
symptom onset. Most (66%) diabetic patients described their pain as “slight”
or “none”, while most (78%) non-diabetics graded their pain as “moderate”
or “severe”. The quality of pain tended to be more distinct in non-diabetics,
while diabetic patients reported mainly shortness of breath. Diabetic patients
were more likely to suffer an in-hospital fatal outcome (8.1% vs. 3.4%), and
were less suitable for single vessel PCI (58% vs. 82%). Earlier arrival times and
cautious evaluation of diabetic patients alone are not enough to significantly
improve overall survival; a multidisciplinary approach is necessary before
neuropathy and irreversible cardiovascular damages set in.
Spearman’s correlation coefficients relating WBC types to metabolic
variables
Neutrophils
Lymphocytes Monocytes
2-h glucose
0.16 *
0.14 *
0.05
Body mass index
0.13 *
0.23 *
0.08 ‡
Insulin sensitivity index
- 0.21 *
- 0.24 *
- 0.10 †C-reactive protein
0.28 *
0.17 *
0.12 *
* p <0.001; †p <0.01; ‡ p <0.05
Lymphocyte count predicted incident diabetes, whereas neutrophil and
monocyte counts did not. SI explained much of the relationship between
lymphocyte count and incidence of diabetes.
OR and 95% CI of incident diabetes by tertiles of WBC type counts
Adjustment model 1st tertile
2nd tertile
3rd tertile
p for
trend
Neutrophils Non-adjusted
Referent 1.27 (0.80, 2.02) 1.48 (0.94, 2.33) 0.088
Monocytes Non-adjusted
Referent 1.30 (0.82, 2.04) 1.23 (0.78, 1.95) 0.373
Lymphocytes Non-adjusted
Referent 1.45 (0.90, 2.33) 1.83 (1.16, 2.91) 0.010
Lymphocytes Demographic,
Referent 1.48 (0.88, 2.50) 1.77 (1.05, 2.98) 0.034
BMI, and glucose
tolerance
Lymphocytes Demographic, BMI, Referent 1.34 (0.78, 2.32) 1.36 (0.78, 2.37) 0.295
glucose tolerance,
and SI
Epidemiology—Clinical—
Diagnosis and Screening
102-LB
In conclusion, lymphocyte count carries prognostic information in terms of
risk of developing diabetes.
The Finnish Diabetes Risk Score in Detecting Undiagnosed Diabetes
and Pre-Diabetes in U.S. Adults by Gender and Race/Ethnicity
Supported by: NHLBI; NCRR GCRC
LU ZHANG, ZHENZHEN ZHANG, GANG HU, YURONG ZHANG, New Orleans, LA,
East Lansing, MI, Baton Rouge, LA, Xi’an, China
104-LB
This study aimed to evaluate the Finnish Diabetes Risk Score (FINDRISC)
in detecting the undiagnosed diabetes and pre-diabetes in U.S. adults and to
examine whether there was a gender and racial/ethnic difference. This crosssectional analysis included 20,633 adults (≥ 20 years of age) who participated
in the National Health and Nutrition Examination Survey (NHANES) 19992010, consisting of 49.8% women, 53.0% non-Hispanic White, 18.1% nonHispanic Black and 24.9% Hispanics. The overall prevalence (weighted) of
undiagnosed diabetes (fasting glucose ≥ 126 mg/dl, HbA1C ≥ 6.5%, or glucose
≥ 200 mg/dl on a 2-h oral glucose tolerance test [OGTT]) and pre-diabetes
(fasting glucose between 100 and 125 mg/dl, HbA1C between 5.7 and
6.4%, or glucose between 140 and 199 mg/dl on a 2-h OGTT) was 4.1% and
35.5%, respectively. FINDRISC (range: 0-26) was positively associated with
the prevalence of diabetes (OR=1.49, p< 0.001) and pre-diabetes (OR=1.15,
An Evaluation of the Ipswich Touch Test for Peripheral Neuropathy
Screening in a Developing Country: A Comparative Study
ZULFIQARALI G. ABBAS, JANET LUTALE, LENNOX K. ARCHIBALD, Dar es Salaam,
United Republic of Tanzania, Gainesville, FL
Diabetic foot ulcers (DFU) are associated with substantial morbidity and
mortality in persons with diabetes in in Dar es Salaam, Tanzania. Peripheral
neuropathy (PN) is the major risk factor for DFU in this population. Thus,
sensitive screening methods are desirable to identify at-risk persons. Recently,
the Ipswich Touch Test (IpTT) was touted as a sensitive, user-friendly screening
method for PN in settings with limited resources. Thus, we carried out this
study to determine the utility of the IpTT for PN screening in Dar es Salaam
when compared with three standard methods: (i) monofilament (MF); (ii)
For author disclosure information, see page LB66.
ADA-Funded Research
LB28
Epidemiology/Genetics
vibration perception threshold (VPT); and (iii) hot/cold perception threshold
(HCPT). We studied consecutive persons attending a large diabetes clinic in
Dar es Salaam. The IpTT involved touching the tips of the 1st, 3rd, and 5th toes
and dorsum of the hallux with tip of index finger for 1-2 s. Pressure sensation
on these toes was assessed with 10-g MF applied for 1-2 s. VPT was measured
bilaterally in the wrists, knees, ankles, and halluces by biothesiometry. HCPT
was ascertained in 1st, 3rd, and 5th toes, heel, and plantar surfaces with a
sensitometer. Of 671 individuals screened, 579 (86%) were ethnic Africans, 8%
Asian Indians, and 6% Arabs. Median age was 52 (range: 17-90) years; median
duration of diabetes (DOD) was 5 (range: 1-40) years. Overall PN prevalence
by HCPT, VPT, MF, IpTT was 89%, 50%, 38%, and 10%, respectively. Using
HCPT as the gold standard, the overall sensitivity of VPT, MF, IpTT was 53%,
42%, and 12%, respectively. The sensitivity of VPT for each DOD quartile was
37%, 41%, 69%; the corresponding sensitivity of MF was 40%, 36%, and 47%,
respectively. In conclusion, the IpTT was not useful as a screening test for PN
because of relatively low sensitivity. HCPT demonstrated a high prevalence
of PN in the diabetes population in Dar es Salaam, did not vary much with
duration of diabetes as VPT, and is therefore a better gold standard than VPT
or IpTT for ascertaining DFU risk.
(Table). Other significant predictive variables included length of index stay,
A1C testing, and pre-period emergency room visits. These data highlight the
importance of appropriate recognition of and treatment for T2DM prior to and
during a hospitalization as well as encounters with the healthcare system
following discharge in predicting a subsequent hospitalization.
Variable
Treatment escalation
Insulin-to-insulin
None-to-insulin
None-to-oral
Oral-to-insulin
Oral-to-oral
No treatment escalation
Region
Northeast
Midwest
West
Other
South
T2DM diagnosis status
Diagnosed diabetes
Undiagnosed diabetes
Pre-period CHF diagnosis
No
Yes
Variable
Adjusted OR (95% CI)
OR vs. no escalation:
3.134 (2.715-3.618)
69.225 (59.120-81.056)
8.338 (6.893-10.087)
35.549 (28.435-44.442)
1.073 (0.905-1.272)
NA
OR vs. South:
33
6.1 (2)
1.368 (0.316-5.919)
15,981
10.6 (1,689)
1.635 (1.442-1.853)
2,620
13.2 (347)
1.201 (1.015-1.421)
1,052
33.2 (349)
4.356 (3.647-5.202)
11,929
9.6 (1,144)
NA
OR vs. undiagnosed:
21,074
11.5 (2,432)
0.514 (0.463-0.570)
10,541
10.4 (1,099)
NA
OR vs. no CHF:
28,586
10.3 (2,948)
NA
3,029
19.2 (583)
1.606 (1.421-1.815)
Not
Readmitted, Adjusted OR (95% CI),
readmitted,
mean
not readmitted vs.
mean (SD)
(SD)
readmitted
Pre-period emergency room visits 0.61 (1.72)
0.96 (2.74)
1.058 (1.040-1.076)
Post-period non-inpatient visits 3.85 (4.14)
5.40 (7.07)
1.040 (1.032-1.049)
Index length of stay, days
4.17 (5.04)
5.60 (6.00)
1.039 (1.028-1.049)
Abbreviations: CHF=congestive heart failure; CI=confidence interval; NA=not applicable;
OR=odds ratio; SD=standard deviation; T2DM=type 2 diabetes mellitus.
105-LB
Pancreatic Regenerating Protein: A New Predictor for the Development
of Type 2 Diabetes and Diabetic Chronic Complications
JIAYUE YANG, ZILIN SUN, ROLF GRAF, LING LI, Nanjing, China, Zurich, SwitzerВ­
land
Type 2 diabetes mellitus (T2DM) is one of the most common non-comВ­
municable diseases globally, and its complications result in increasing disability,
reduced life expectancy and enormous health costs. However, it is frequently
not diagnosed until complications occur. Pancreatic regenerating protein (reg)
is mitogenic to islet ОІ-cells and associated with inflammation, while no data
exist regarding the prognostic value of reg among T2DM patients. The aim
of this pilot study was to evaluate the quantity of reg in different clinical
stages of T2DM and its correlation with diabetic complications. We analysed
serum reg and its correlation with clinical and biochemical parameters in 1004
subjects with T2DM at different clinical phases. reg values were measured by
a newly developed ELISA. reg was correlated with the duration of diabetes
(spearman’s rank correlation coefficient 0.319 p<0.001). Compared to healthy
controls, reg levels were elevated in high-risk patients (18.7[15.0-26.4] vs.
16.4[13.9-20.8], p=0.014), and patients with long-term diabetic mellitus
(without complications: 26.4[17.4-38.2] vs. 16.4[13.9-20.8] p<0.001; with
complications: 32.1[22.1-55.5] vs. 16.4[13.9-20.8] p<0.001). Interestingly, there
is no statistically significant differences among the population of high-risk,
IGR and incipient diabetic patients. The area under the curve (AUC) of reg for
incidence of diabetes-onset and chronic complications were 0.640 and 0.754,
separately. Two reg cut-offs potentially allow to identify individuals with a high
risk to develop T2DM and its chronic complications. reg levels above 22 ng/
ml in nondiabetes were associated with a high risk to develop T2DM in future,
levels above 29 ng/ml among T2DM were the most significant parameter to
predict the occurrence of diabetic chronic complications. reg might evolve as
a promising new marker to predict the occurrence, development of T2DM and
diabetic chronic complications.
Total N
—
2,963
1,282
675
446
3,937
22,312
% Readmitted (n)
—
15.2 (450)
75.4 (966)
28.6 (193)
56.7 (253)
4.8 (190)
6.6 (1,479)
Epidemiology—Nutrition
107-LB
Vitamin C and E Supplementation and Risk of Type 2 Diabetes in Men:
Results from the Physicians’ Health Study II Randomized Controlled
Trial
YIQING SONG, LU WANG, JOANN E. MANSON, ROBERT J. GLYNN, JULIE E.
BURING, J. MICHAEL GAZIANO, HOWARD D. SESSO, Boston, MA
Background: Laboratory experiments and human observational studies
have suggested potential benefits of antioxidant vitamins C and E in reducing
the risk of type 2 diabetes. Direct evidence from randomized trials has been
limited, however, especially among men.
Objective: To assess the direct effect of long-term vitamin C and E supplementation
on the incidence of type 2 diabetes in a randomized factorial trial of men.
Design: In the Physicians’ Health Study II randomized trial, a total of
14,641 U.S. male physicians initially aged 50 years and older were randomly
assigned to receive vitamin C (500 mg ascorbic acid daily) and vitamin E (400
IU synthetic a-tocopherol every other day) or their respective placebos, and
followed between 1997 and 2007.
Results: During a mean follow-up of 7.5 years, 775 incident cases of type
2 diabetes were diagnosed based on annual follow-up questionnaires among
13,651 men who were free of diabetes at baseline. There was no overall effect
of vitamin C (relative risk [RR], 1.13; 95% CI, 0.97-1.31 [P=0.11]) or vitamin E
(RR, 0.94; 95% CI, 0.81-1.09 [P=0.38]) on risk of type 2 diabetes. There was no
evidence that diabetes risk factors, including age, body mass index, physical
activity, alcohol intake, smoking status, or parental history of diabetes,
modified the effects of vitamin C or vitamin E on the risk of developing type
2 diabetes. No significant interactions were observed between vitamin C and
vitamin E on diabetes risk. These results remained unchanged after excluding
either non-compliant participants or incident diabetes cases that occurred in
the first two years of follow-up.
Conclusions: This large-scale, long-term randomized trial showed no overall
effects of vitamin C or vitamin E on risk of developing type 2 diabetes in
initially healthy men. These data do not support the use of these antioxidant
supplements for the prevention of type 2 diabetes.
Supported by: NSFC (81270010), (30900696)
Epidemiology—Diabetes Complications
106-LB
Predictors of 30-Day Hospitalization Readmissions in Patients With
Type 2 Diabetes Mellitus (T2DM): A Retrospective Database Study
ELIZABETH EBY, CHRISTINE HARDWICK, MARIA YU, STEVE GELWICKS, KETRA
DESCHAMPS, TOM GEORGE, Indianapolis, IN, Detroit, MI
To understand factors predictive of 30-day hospital readmissions among
patients with T2DM, this retrospective study used 2009-2011 deidentified
Humedica U.S. electronic medical record data to identify patients ≥21 years
old with ≥6 months of data prior to index hospitalization (pre-period) and
≥31 days of data post-discharge (post-period). Stepwise logistic regression,
including demographics, clinical characteristics, and index hospitalizations,
was used to identify factors associated with readmission. Among 31,615
patients with T2DM and an initial hospitalization for any reason, 3,531 (11.2%)
were readmitted within 30 days and 28,084 (88.8%) were not. Most patients
were 65 or older (56.4%), female (55.7%), Caucasian (60.6%), resided in the
Midwest (50.5%), and were on no observed pre-period antidiabetic treatment
agents (76.8%). Diabetic treatment escalation, region, T2DM diagnosis,
pre-period congestive heart failure diagnosis, and number of post-period
non-inpatient healthcare visits were the strongest predictors of readmission
For author disclosure information, see page LB66.
ADA-Funded Research
LB29
Epidemiology/Genetics
108-LB
Epidemiology—Other
Alcohol Consumption, Plasma Fetuin-A and Risk of Type 2 Diabetes
in Women
110-LB
SYLVIA H. LEY, QI SUN, MONIK C. JIMENEZ, KATHRYN M. REXRODE, JOANN E.
MANSON, MAJKEN K. JENSEN, ERIC B. RIMM, FRANK B. HU, Boston, MA
The Risk of Fractures after Initiating Oral Anti-Diabetic Drugs: Results
from the National Claim Registry
Benefits of moderate alcohol consumption on type 2 diabetes have been
well-documented and postulated to involve a mechanism of improved insulin
sensitivity. Fetuin-A, a liver-derived protein that inhibits insulin signaling, has
emerged as a biomarker associated with type 2 diabetes risk. Therefore, alcohol
intake may influence circulating fetuin-A concentrations and subsequently
diabetes risk through altering insulin signal. We hypothesized that moderate
alcohol consumption would be associated with lower plasma fetuin-A and that
fetuin-A would partly explain the association between alcohol consumption
and type 2 diabetes in mid-aged and older women. Multiple linear regression
was conducted among the Nurses’ Health Study female participants with
measures of plasma fetuin-A and alcohol consumption (n=1381). The
proportion of alcohol consumption and type 2 diabetes association explained
by fetuin-A was assessed within 470 matched incident diabetes case-control
pairs from 2000 to 2006. Higher total alcohol intake was associated with lower
plasma fetuin-A (p-trend=0.006): Least-squares meansВ±SE 476.8В±5.7Вµg/mL for
abstainers, 469.0В±5.1 Вµg/mL for 0.1-4.9 g/d consumers, 456.4В±6.9 Вµg/mL for
5.0-14.9 g/d, and 449.3±9.2 µg/mL for ≥15 g/d. The association between alcohol
consumption and diabetes explained by fetuin-A and fasting insulin were 18.3
% (95% CI 0.1-36.4) and 65.2 % (14.7-115.6) (both p-contribution<0.05), while
liver enzymes were not a significant contributor of this association. Further,
fasting insulin explained 61.7 % (25.7-97.8) of the association between fetuin-A
and diabetes (p-contribution=0.0008). In conclusion, moderate total alcohol
consumption is associated with lower plasma fetuin-A concentrations in
women. Fetuin-A and insulin explain a significant proportion of the association
between alcohol consumption and type 2 diabetes in this population. Further
studies are needed to determine whether there are biological mechanisms
underlying this association.
HYUNG JIN CHOI, CHANMI PARK, YOUNG-KYUN LEE, YONG-CHAN HA, SUNMEE
JANG, CHAN SOO SHIN, Cheongju Si, Chungcheongbuk-Do, Republic of Korea,
Seoul, Republic of Korea, Seongnam, Republic of Korea, Gimhae-si, Republic of
Korea
Thiazolidinedione (TZD) increases fracture risk. However, the effect of
other oral anti-diabetic drugs (OADs) on fracture risk is not well known. We
examined the risk of fractures after initiating OADs using the nationwide
database of medical and pharmacy claims in South Korea. Among 2,886,555
subjects with antidiabetes prescriptions, 207,558 subjects aged 50 years and
older, who initiated OADs from January 2008 to June 2011, were analyzed.
Based on medication possession ratio data, subjects were classified as
a non-user, metformin alone, sulfonylurea (SU) alone, alpha-glucosidase
inhibitor alone, metformin+SU combination, metformin+TZD combination,
metformin+DPP4 inhibitor combination and SU+TZD combination. The outcome
measure was the first occurrence for a vertebral fracture or a non-vertebral
fracture. The incidence of fracture was analyzed controlling for age, gender,
comorbidity score, diagnosis of osteoporosis, osteoporosis treatment, and
osteoporosis related diseases. Total of 5,996 fractures were observed among
207,558 subjects during the observation period. Fracture rate per 10,000
person-years varied significantly across type of OADs, with metformin+DPP4
inhibitor combination group having the lowest rate [124.9, 95% confidence
interval (CI) 106.0-147.1] and SU+TZD combination group having the highest
rate (269.6, 95% CI 222.1-327.4). Metformin+DPP4 inhibitor combination group
had significantly reduced fracture risk compared with non-users [hazard ratio
(HR)=0.83, 95% CI 0.70-0.98, P=0.025]. In models adjusting for all confounding
factors, metformin+DPP4 inhibitor combination group showed a trend of lower
non-vertebral fracture risk compared with metformin+SU combination group
(HR=0.82, 95% CI 0.65-1.03, P=0.086). TZD was significantly associated with
increased risk of fracture (HR=1.59, 95% CI 1.38-1.82), P&lt;0.001). These
findings suggest that DPP4 inhibitor may have a protective effect on bone
metabolism.
Supported by: NIH; CIHR
109-LB
Prospective Study of Fast-Food Consumption and the Risk of GestationВ­
al Diabetes: The SUN Cohort
FRANCISCO JAVIER BASTERRA-GORTARI, LIGIA J. DOMINGUEZ, MIGUEL ANGEL
MARTINEZ-GONZALEZ, ALFREDO GEA, CARMEN DE LA FUENTE, LLUIS FORGA,
MAIRA BES-RASTROLLO, Pamplona, Spain, Palermo, Italy
111-LB
Dipeptidyl Peptidase 4 Inhibitors and Comparative Pancreatic Cancer
Risk
Little is known about the influence of fast-food consumption on incident
gestational diabetes mellitus (GDM). Therefore, our objective was to evaluate
the association between fast-food consumption and GDM in a cohort of
university graduates.
The prospective dynamic SUN cohort included data of 2903 women free
of diabetes or previous GDM who reported at least one pregnancy between
1999 and 2010. Fast-food consumption was assessed through a validated
semi-quantitative food frequency questionnaire. Fast-food was defined as the
consumption of hamburgers, sausages, and pizza. Three categories of fastfood were established: low (0-3 servings/month), intermediate (>3 servings/
month-2 servings/week) and high (>2 servings/week). Non-conditional logistic
regression models were used to adjust for potential confounders.
We identified 169 incident cases of GDM during follow-up. After adjusting
for age, baseline body mass index, smoking, physical activity, alcohol intake,
fiber intake, Mediterranean dietary pattern, soft drinks consumption, family
history of diabetes, cardiovascular disease and hypertension at baseline, and
parity, regular fast-food consumption was significantly positively associated
with incident GDM. Women in the intermediate category of consumption had
an adjusted OR of 1.35 (95% CI 0.84-2.17) and those in the highest category
had an adjusted OR of 1.77 (95% CI: 1.08-2.91) compared with the low
consumption group; p for linear trend: 0.018.
Our results suggest that pre-pregnancy higher consumption of fast-food
(defined as the consumption of hamburgers, sausages, and pizza) was a risk
factor for GDM.
MUGDHA GOKHALE, TIL STURMER, CHRIS GRAY, VIRGINIA PATE, ALISON
MARQUIS, JOHN B. BUSE, Chapel Hill, NC
A recent study analyzing human pancreata described potentially detrimental
effects of sitagliptin, a dipeptidyl peptidase 4 inhibitor (DPP4i), on human
pancreas with implications for incident pancreatic cancer (PC). This adds to
concerns raised by an analysis of the FDA Adverse Events Reporting System
which reported increased PC rates with incretin-based drugs. Both studies are
limited by many shortcomings. We compared PC risk after initiation of DPP4i
versus sulfonylureas (SU) and thiazolidinediones (TZD) using a 20% sample of
the 2006-10 Medicare claims. To address concerns about potential outcome
detection bias, we compared the cumulative incidence of diagnostic work-up
in the two cohorts before and after initiation (index date). This was a new user
active comparator cohort study consisting of patients &gt;65 years requiring a
second prescription of the same drug within 180 days of initiation with followup starting at the second fill date. Using an as-treated approach, we used
propensity score adjusted Cox models to estimate hazard ratios (HR) and 95%
confidence intervals (CI). Diagnostic work-up pre and post index was compared
using risk ratios (RR). There were 19294 DPP4i initiators with mean age 74. Over
a 9 month median follow-up, 29 DPP4i initiators had a PC diagnosis. The hazard
of PC with DPP4i was lower relative to SU (HR 0.5, CI 0.3 - 1.0) and similar to
TZD (HR 1.1, CI 0.7 - 1.8). Excluding the first 9 months after drug initiation to
reduce the potential for reverse causality did not alter results. In the 6 months
post index, the cumulative incidence of diagnostic work-up among sitaglitpin
initiators (79.4%) was similar to TZD (74.0%) (RR 1.07, CI 1.06 - 1.08) and
SU (74.6%) (RR 1.06, CI 1.05 - 1.07). The probability of diagnostic workup pre
index was similar for all groups (~80%). Though limited by sample size and real
world duration of treatment, contrary to previous evidence, our data suggest
no increased pancreatic cancer risk with DPP4i relative to SU or TZD and that
diagnostic work-up is not affected by DPP4i use.
Supported by: Spanish Government (PI10), (02293); Navarra Government (45/2011)
For author disclosure information, see page LB66.
ADA-Funded Research
LB30
Epidemiology/Genetics
112-LB
Combination Therapy With Metformin Plus Sulfonylureas versus
Metformin Plus DPP-4 Inhibitors and Risk of All-Cause Mortality
Metformin Effects on High- vs. Low-Grade Prostate Cancer
114-LB
CHEN-PIN WANG, JAVIER HERNANDEZ, CARLOS LORENZO, BRAD POLLOCK,
DONNA LEHMAN, San Antonio, TX
CRAIG J. CURRIE, SARA JENKINS-JONES, JAYANTI MUKHERJEE, CHRISTOPHER
L.L. MORGAN, Cardiff, United Kingdom, Wallingford, CT
While several in vitro studies suggested that metformin may reduce the
risk of prostate cancer (PCa), epidemiologic studies have been inconclusive. A
recent case control study suggested that metformin may slow PCa progression.
We investigate whether the effect of metformin on low-grade PCa incidence
differs from that on high-grade PCa in men with type 2 diabetes (T2DM).
We conducted a historical longitudinal study using a clinical cohort seen at
the VA October 2002-September 2012. The cohort included men ≥40 years old,
with T2DM, without statin use, and no cancer history. They either had metformin
prescriptions ≥180 days, or were never on any diabetes medication. Cox
proportional regression adjusting for covariates and the propensity for metformin
use was used to estimate the hazard ratio (HR) of PCa due to metformin use.
The cohort included 13409 men with T2DM, where 2490 were metformin
users. There were 423 low-grade PCa cases and 87 high-grade PCa cases.
Overall, metformin was not increase the risk of PCa (HR=1.07, 95% CI: 0.95–
1.21; p=0.266). Metformin was associated with an increased risk of low-grade
PCa (HR=1.14, 95% CI: 0.99–1.30; p=0.053), and a decreased risk of highgrade PCa (HR=0.75, 95% CI: 0.55–1.02; p=0.067). The differential effect of
metformin on high- vs. low-grade PCa was statistically significant (p=0.007).
The heterogeneity of metformin’s pleiotropic effects on high- and low-risk
PCa needs to be corroborated by large clinical trials.
Aims: The aim of this study was to evaluate the risk of all-cause mortality
for patients exposed to dual therapy with metformin and sulfonylureas (SUs)
vs. metformin and DPP-4 inhibitors (DPP-4i).
Materials and methods: Retrospective data were extracted CPRD: a data
resource comprising approximately 10% of patients treated in primary care
in the UK. Patients with type 2 diabetes initiated with treatment comprising
metformin with either a SU or a DPP-4i between 2007 and 2012 were included,
regardless where these regimens were used in the natural history of the
disease. Time to all-cause mortality was compared using Cox proportional
hazards models. In addition to the main comparative analysis adjusting for
key covariates within the model, two additional sensitivity analyses were
performed. Firstly, a matched-cohort study using the following matching criteria
at baseline: age (В±2 years), gender, diabetes duration (В±1 year), BMI (В±3 Kg/
m2), serum creatinine (В±10 Ојmol/L) and HbA1c (В±1%). Secondly, patients were
also matched by propensity score predicted by the same candidate variables.
Results: In the main analysis, 27,251 patients were prescribed metformin in
combination with a SUs, and 5,215 were prescribed metformin in combination
with a DPP-4i. 3,454 patients were included in each arm of the direct matched
cohorts and 4,703 in each arm in the propensity matched analysis. With
respect to all-cause mortality, in the main analysis the adjusted hazard ratio
(aHR) was increased using SUs (aHR=1.265, 95%CI 0.900-1.779). The aHR was
significantly increased for metformin+SUs compared with metformin+DPP-4i
for those matched directly (aHR=2.314, 1.348-3.973) and those matched on
propensity score (aHR=1.691, 1.135-2.519).
Conclusion: There was a consistent reduction in mortality for patients
prescribed metformin in combination with DPP-4i versus metformin in
combination with SUs. These data should be considered when initiating dual
therapy with metformin.
Non-Metformin (n=10919) Metformin (n=2490)
mean
s.d.
mean
s.d.
study length (days)
2280.60
1300.36
2266.31 1146.93
low-grade PCa (%)
3.10
3.41
high-grade PCa (%)
0.66
0.60
age
69.85
10.87
67.23
11.06
Black (%)
18.12
19.00
Hispanic (%)
4.77
7.07
baseline A1c
6.34
1.35
6.59
0.95
mean A1c
6.29
1.34
6.48
1.27
baseline LDL
100.59
28.26
95.84
25.82
mean LDL
91.60
27.16
88.69
24.49
baseline BMI
30.31
62.25
30.79
6.11
mean BMI
29.25
62.00
29.30
6.19
baseline comorbidity
4.75
2.77
3.87
2.20
mean comorbidity
3.62
2.69
3.37
2.60
В Supported by: Bristol-Myers Squibb
113-LB
42-Months Intervention on Glucose Control and End Events in Type
2 Diabetes Patients With Different Level of Education in Beijing
Communities
GUANG-RAN YANG, MINGXIA YUAN, GANG WAN, SHENYUAN YUAN, HANJING
FU, LIANGXIANG ZHU, SUFANG PAN, RONGRONG XIE, YUJIE LV, NING ZHUANG,
XUEPING DU, YULING LI, YU JI, XIAONING GU, YUE LI, Beijing, China
To investigate the effects of educational level on glucose control and end
events after 42-months intervention in type 2 diabetes patients in Beijing
communities.
Using multi-stage sampling, 2,866 type 2 diabetes patients from 15
Beijing urban communities were investigated. After 42-months intervention,
end events including the incidence of macrovascular complications (such as
myocardiac infarction, heart failure, cerebral infarction and stroke), malignant
tumors and aggravation of diabetic nephropathy were recorded. Educational
attainment was categorized into three levels: low (elementary school or
illiteracy), medium (middle school) and high (college or academic degree).(1) At
baseline, the numbers of patients reaching good glucose control (HbA1c ≤7.0
%) in the low, medium and high educational group were 49.09%, 54.82% and
62.59%, respectively (P<0.001). (2) Logistic analysis showed that after adjusted
for confounding factors, educational level was independently associated with
glucose control(medium OR=0.772, High OR=0.589, p all <0.05). (3) After
42-month intervention, 2637 people were followed up. Fasting plasma glucose
and HbA1c reached the highest in the low educational group (7.51В±2.05
mmol/L, 7.20В±1.27 %, respectively). The numbers of patients reaching good
glucose control (HbA1c ≤7.0 %) in the low, medium and high educational group
were 49.09%, 54.82% and 62.59%, respectively. The incidence of end events
among the three educational level groups was 4.5%, 2.4% and 1.5%. (4) Cox
regression analysis showed that educational level was related to the incidence
of end events(medium HR=0.572, High HR=0.351, p all <0.05).It showed that
the educational level was found to be associated with glucose control after
42-months intervention. Educational attainment seems to be related with the
incidence of macrovascular complications, malignant tumors and aggravation
of renal disease in type 2 diabetes in Beijing.
Supported by: 1R21CA161180-01
Epidemiology—Type 1 Diabetes
Prevalence of Diabetes in Veterans Stratified by Gender
115-LB
JOSEPH FINKELSTEIN, EUNME CHA, Baltimore, MD
Background: Despite the large number of epidemiological data available
on the high prevalence of diabetes, a paucity of studies explored the risk of
diabetes in the veteran population.
Methods: The Integrated Health Interview Series (IHIS) is a harmonized data
for the U.S. National Health Interview Survey (NHIS). Based on the IHIS 19972010 dataset, population-based prevalence of diabetes among veterans were
compared to non-veteran civilians, further stratified by gender. Regression
models were performed to evaluate the association between the veteran
status and the risk for diabetes. Veteran status was defined if a participant
answered �Yes’ to the question, “Have you ever been honorably discharged
from active duty in the U.S. Army, Navy, Air Force, Marine Corps, or Coast
Guard?” Diagnose of diabetes was self-reported including those who were in
the borderline. Statistical analyses were performed by SAS version 9.0.
Results: From 1997 to 2010, overall 13.8% of veterans reported to have
diabetes compared to 7.7% of non-veteran civilians (Rao-Scott chi square,
p<.0001). Among men, 14.3% of veterans and 6.6% of civilians had diabetes
(Rao-Scott chi square, p<.0001). For females, prevalence of diabetes (6.7%)
was lower in veterans than civilians (8.4%) with statistical significance.
Adjusting for age, race, marital status, Body Mass Index (BMI), alcohol
drinking, education, poverty level, smoking and exercise, a regression model
showed that male veterans were 1.4 times more likely to have diabetes than
Supported by: Capital Medical Development Foundation of China
For author disclosure information, see page LB66.
ADA-Funded Research
LB31
Epidemiology/Genetics
non-veteran civilians (OR 1.4 95% CI: 1.4-1.5). For females, veterans had 10%
less risk for diabetes than civilians but with no statistical significance (OR 0.9
95% CI: 0.7-1.1).
Conclusion: Overall the prevalence of diabetes was higher in male veterans
than non-veteran civilians. This association remained significant after adjusting
for socio-demographic and health behavior factors.
significant in all 3 samples (see table). Interestingly, the smaller sets of muscle
and adipose eQTLs accounted for more of the variance in T2D liability (with
stronger statistical significance) in the SC and MC GWAS than was observed
using all SNPs. These results support our hypothesis that common eQTLs
mapped in insulin-responsive tissues account for a substantial portion of the
variance in liability to T2D.
Dataset
Cases
(n)
Controls
(n)
Total В±
SE (%)
Muscle В±
SE (%)
SC
MC
WTCCC
837
965
1924
781
345
2938
58 В± 16
77В± 23
55 В± 5
75 В±16
84 В± 22
39 В± 4
Genetics—Type 2 Diabetes
116-LB
SNPs in ADAMTS7, the 9p21 Region and UBE2E Interact With Type 2
Diabetes Status to Modify the Risk of Coronary Artery Disease
NIGEL W. RAYNER, NATALIE VAN ZUYDAM, BENJAMIN F. VOIGHT, CLAES
LADENVALL, RONA J. STRAWBRIDGE, SARA M. WILLEMS, ERIK P.A. VAN
IPEREN, JAANA HARTIALA, EFTHYMIA VLACHOPOULOU, EVELIN MIHAILOV,
LYDIA KWEE, CHRIS NELSON, LIMING QU, ANUJ GOEL, MARCUS KLEBER,
JITENDER KUMAR, STAVROULA KANONI, CARDIOGRAMPLUSC4D, SUMMIT,
Oxford, United Kingdom, Dundee, United Kingdom, Philadelphia, PA, Malmö,
Sweden, Stockholm, Sweden, Rotterdam, Netherlands, Amsterdam, Netherlands,
Los Angeles, CA, Helsinki, Finland, Tartu, Estonia, Durham, NC, Leicester, United
Kingdom, Heidelberg, Germany, Uppsala, Sweden, Cambridge, United Kingdom
Adipose В± Percent of Muscle
SE (%) (Adipose) eQTLs out
of Total Set
63 В± 16
75 В± 23
40 В± 5
15 (18)
16 (18)
15 (17)
118-LB
TCF7L2 Overexpression and Type 2 Diabetes: Dissecting the Function
of Tcf7l2 as a Regulator of Glucose Metabolism
KATHLEEN A. BAILEY, SOO-YOUNG PARK, JERRY KILIMNIK, MANAMI HARA,
PIOTR WITKOWSKI, GRAEME I. BELL, MARCELO NOBREGA, Chicago, IL
Genome-wide association studies to identify variants associated with type
2 diabetes (T2D) consistently identify a region of non-coding variation within
transcription factor 7-like 2 (TCF7L2). To test if variation in this region could
cause a change in TCF7L2 expression leading to T2D risk, we recombineered
additional copies of Tcf7l2 into the mouse leading to global overexpression.
Intraperitoneal glucose tolerance test (IPGTT) on these overexpression
mice identified glucose intolerance, highlighting a role for Tcf7l2 in glucose
homeostasis.
Global overexpression of Tcf7l2 in the mouse leads to glucose intolerance
but does not explain the tissue-specific mechanism by which overexpression
leads to hyperglycemia. To isolate the effect of Tcf7l2 overexpression in each
tissue, we restore wildtype expression in a single tissue using a Cre-loxP
system and look for rescue of the glucose intolerance phenotype.
We first restored normal Tcf7l2 expression in beta-cells while maintaining
overexpression elsewhere. Using IPGTT, we discovered normal expression
in beta-cells led to more severe hyperglycemia compared to global overВ­
expression. Perifusion on isolated islets indicated that beta-cells with Tcf7l2
overexpression secrete more insulin than beta-cells with wildtype expression.
Immunohistochemistry found that global overexpression mice have a larger
beta-cell area than mice with normal expression in beta-cells.
We compared mice with global overexpression of Tcf7l2 and mice with
normal expression in beta-cells but overexpression elsewhere. When we
restore normal Tcf7l2 expression in beta-cells, we decrease beta-cell area, we
reduce insulin secretion, and we increase hyperglycemia. These data suggest
that Tcf7l2 overexpression in beta-cells protects against T2D rather than
causing glucose intolerance. It also points to a mechanism in the periphery
as responsible for the glucose intolerance seen in T2D patients harboring the
TCF7L2 risk variants.
Patients with type 2 diabetes (T2D) are 3-4 times more likely to suffer from
coronary artery disease (CAD). Despite this no overlapping loci between CAD
and T2D have been identified to date. In this study we aimed to: identify loci
that modify the risk of CAD in patients with T2D, assess whether known CAD
loci have a different effect on CAD risk in patients with T2D and evaluate the
influence of known T2D loci on CAD risk in non-diabetic individuals compared
to patients with T2D.
Summary statistics for 2,295,146 SNPs from 16,942 patients with T2D (6,022
CAD cases and 10,920 CAD free controls) and 28,727 non-diabetic individuals
(10,892 CAD cases and 17,835 CAD free controls) were combined in a fixed
effects meta-analysis and stratified by T2D status.
The meta-analysis of SNP effects on CAD in patients with T2D identified
associations in ADAMTS7 represented by two independent SNPs previously
reported for CAD. Rs11072811 (Odds Ratio (OR)=1.17, effect allele frequency
(EAF) = 0.53, p=3.9E-11) and rs11634042 (OR=1.15, EAF =0.58, p=5.7E-08):
rs11072811 had a smaller effect on CAD risk in non-diabetic individuals
(OR=1.08, p=1.2E-02) when compared to its effect in patients with T2D, and
this interaction with T2D status was nominally significant (p=3.5E-02).
Rs1556516, a proxy for the known CAD SNP rs1333049 in the wellestablished 9p21 locus, had a smaller OR in patients with T2D (T2D OR=1.10,
p=3.9E-03 and non-diabetic OR=1.17, p=2.9E-10) and this was nominally
significant for interaction (p=4.2E-02).
Investigation of the known T2D-risk loci revealed that the major allele
(frequency=0.89) of rs7612463, in UBE2E2, decreased the risk of CAD in
patients with T2D (OR=0.86, p=7.4E-03) but increased the risk of CAD in nondiabetic individuals (OR=1.11, p=3.7E-02). This interaction was significant after
Bonferroni correction (p=7.2E-04).
This study suggests known CAD SNPs in ADAMTS7 and 9p21, and known
T2D SNPs in UBE2E may differentially modify CAD risk based on T2D status.
119-LB
Pleiotropic Effects on Lipid Levels and Obesity Identified in Multi-Trait
Meta-Analysis of Genome-Wide Association Studies (GWAS) of Type
2 Diabetes (T2D) Related Traits
Supported by: Innovative Medicines Initiative
117-LB
INGA PROKOPENKO, VASILIKI LAGOU, REEDIK MГ„GI, IDA SURAKKA, ANTTIPEKKA SARIN, MOMOKO HORIKOSHI, LETIZIA MARULLO, TERESA FERREIRA,
GUDMAR THORLEIFSSON, SARA HГ„GG, MARIAN BEEKMAN, CLAES LADENVALL,
ANUBHA MAHAJAN, JOUKE-JAN HOTTENGA, JANINA RIED, THOMAS
W. WINKLER, CHRISTINA WILLENBORG, MARK I. MCCARTHY, ANDREW P.
MORRIS, SAMULI RIPATTI, THE ENGAGE CONSORTIUM, London, United Kingdom,
Oxford, United Kingdom, Tartu, Estonia, Helsinki, Finland, Ferrara, Italy, Reykjavik,
Iceland, Stockholm, Sweden, Leiden, Netherlands, Malmö, Sweden, Amsterdam,
Netherlands, Neuherberg, Germany, Regensburg, Germany, LГјbeck, Germany
eQTLs from Skeletal Muscle and Adipose Tissue Account for Most of
the Heritability to Type 2 Diabetes Estimated in Mexican Americans,
Mexicans and Europeans
JASON M. TORRES, ERIC GAMAZON, JENNIFER BELOW, SWAPAN DAS,
HEATHER M. HIGHLAND, ESTEBAN PARRA, ADAN VALLEDARES-SALAGADO,
JORGE ESCOBEDO, MIGUEL CRUZ, CRAIG L. HANIS, NANCY J. COX, Chicago,
IL, Seattle, WA, Winston-Salem, NC, Houston, TX, Toronto, ON, Canada, Mexico
City, Mexico
Previous studies have shown that top signals from genome-wide association
studies (GWAS) on type 2 diabetes (T2D) are enriched for expression quantitative
trait loci (eQTLs) identified in skeletal muscle and adipose tissue. We therefore
hypothesized that such eQTLs might account for a disproportionate share of
the phenotypic variance in liability to type 2 diabetes (T2D) estimated from all
SNPs interrogated through GWAS. To test this hypothesis, we applied genomewide complex trait analysis (GCTA) to GWAS on T2D from Mexican Americans
living in Starr County, TX (SC), and Mexicans from Mexico City (MC), as well as
to the GWAS on T2D from the WTCCC on subjects from the UK. We estimated
the proportion of phenotypic variance attributable to additive effects of all
variants interrogated in these GWAS (i.e. chip-based heritability), as well as
from a much smaller set of variants identified as eQTLs for muscle or adipose
tissue. Estimates of chip-based heritability were appreciable and statistically
Serum lipid levels, fat storage and obesity are related to T2D risk through
shared biochemical pathways and can be influenced by common genetic
factors. Analysis of the genetic effects on multiple phenotypes simultaneously
allows dissection of variable patterns of multi-trait associations.
Within the ENGAGE consortium, we assessed multi-trait genetic effects
on four blood lipids (high-/low-density lipoprotein and total cholesterol,
triglycerides [HDL/LDL/TC/TG]) and body-mass index (BMI). The 1000 Genomes
reference panel (06/2011) was used for imputation in up to 41,752 individuals
from 18 European GWAS. Each study carried out multi-trait analysis by fitting
a multiple logistic regression on SNP genotypes allowing for joint effects of
four lipid traits and BMI. Single-trait meta-analyses, conditional on remaining
traits, were used to verify the independence of trait-specific genetic effects.
For author disclosure information, see page LB66.
ADA-Funded Research
LB32
Epidemiology/Genetics
Joint analysis enabled identification of 26 signals with genome-wide
significant (PLRT<5.0x10-8) multi-trait effects, including 9 loci with associations
(P<5.0x10-8) driven by the individual trait effects: a) TRIB1 on BMI, b) GCKR,
FADS1, MLXIPL on TG; c) CEPT on BMI/HDL, d) LPL, APOA1 on BMI/TG; e)
LIPC on HDL/TG, f) APOE on HDL/LDL/TG. At four loci, where association with
obesity was identified for the first time, higher BMI was related to higher
HDL and lower TG indicating complex relationships between adiposity and
regulation of lipid levels. Effects on lipids at CELSR2, ABCA1, HNF4A, MADD,
PPP1R3B and RANB10 were determined by the association with HDL. At the
remaining 11 pleiotropic loci multiple traits contributed to the signal.
We detected a substantial proportion of loci with complex patterns of
genetic effects, highlighting the importance of modelling multiple T2D-related
metabolic traits simultaneously for dissection of association signals.
four independent SNPs met significance for the joint effect: rs3091258 at the
TNF-LTB locus, rs9267490 in NFKBIL1, rs1115764 in SEZ6L, and rs1019856 in
TGFBR2. For rs1019856 in TGFBR2, the SNP main effect (p=9.8*10-6) seemed
to drive this joint effect, but SNP*smoking interaction (p 3.3*10-5 to 5.8*104) seemed to drive the joint effect of the other three. Variants in SEZ6L and
TGFBR2 have been previously reported to be associated with fasting insulin
and blood pressure, respectively. These results merit replication in larger
studies and may elucidate new causal pathways in smoking and T2D risk.
122-LB
Genome-Wide Association With Fasting Glucose (FG) in 20,000 African
Americans Suggests New Loci and Allelic Heterogeneity at Known
Loci: The African American Glucose and Insulin Genetic Epidemiology
(AAGILE) Consortium
Supported by: FP7-HEALTH-F4-2007
JAMES B. MEIGS, MARIE FRANCE HIVERT, ANDREW P. MORRIS, MAN LI,
MAGGIE NG, JINGMIN LIU, RICHARD A. JENSEN, XIUQING GUO, JEANETTE S.
ANDREWS, LISA R. YANEK, GUANJE CHEN, MICHAEL A. NALLS, LAWRENCE
F. BIELAK, MARGUERITE R. IRVIN, WEI-MIN CHEN, PING AN, EDMOND K.
KABAGAMBE, BRIAN CADE, JAMES G. WILSON, JAEYOUNG HONG, DENIS
RYBIN, CHING-TI LIU, AAGILE INVESTIGATORS, MAGIC INVESTIGATORS,
Boston, MA, Sherbrooke, QC, Canada, Oxford, United Kingdom, Winston-Salem,
NC, Seattle, WA, Los Angeles, CA, Baltimore, MD, Bethesda, MD, Ann Arbor, MI,
Birmingham, AL, Charlottesville, VA, St. Louis, MO, Nashville, TN
120-LB
Variation in Glucose Homeostasis Traits due to P2X7 Polymorphisms
in Mice and Humans
JENNIFER TODD, JOSE C. FLOREZ, VALERIYA LYSSENKO, DAVID FRIEDMAN,
Boston, MA, Malmö, Sweden
ATP, a key molecule in energy metabolism, also acts as an extracellular
signal via two families of purinergic receptors, P2X and P2Y. Both receptor
types are expressed in pancreatic ОІ-cells and ATP is contained in insulin
secretory granules. We hypothesized that purinergic signaling might influence
glucose regulation.
We generated a mouse model of purinergic signaling dysfunction by crossing
129SvJ mice with C57BL6 mice that have a naturally hypomorphic P2x7 variant
(P451L). There were no significant differences in weight, fasting glucose, or
fasting insulin for mice with the two different P2x7 alleles at baseline. On
glucose tolerance testing (GTT) in 8-week old females, area under the curve
was 17% larger for P2x7-C57 vs. P2x7-129 mice (P<0.05); and at 16-20 weeks,
13% larger (P<0.05). On insulin tolerance testing (ITT), area above the curve
was 27% larger (P<0.005) for P2x7-C57 females. Similar results on GTT and
ITT were seen for males.
In humans, we mined the Meta-Analysis of Glucose and Insulin-Related
Traits Consortium (MAGIC) and Diabetes Genetics Replication and Metaanalysis (DIAGRAM) Consortium databases to examine purinergic signalling
genes for association with glycemic traits and type 2 diabetes risk, respectively.
We found associations of one SNP each in 5 genes with glycemic traits and
14 SNPs in 3 genes withT2D risk, using an a priori significance level based on
the number of independent tests per gene. Testing these along with common
missense variants in the Botnia Primary Prevention Program (n=3,000), we
found a strong association for rs1718119 in P2RX7: carriers of the minor
(A) allele have increased insulin sensitivity, increased insulin release, and
improved disposition index. This SNP encodes an A348T amino acid change
shown to have increased pore function compared to the major allele.
Together, our data show association of the purinergic signaling pathway
in general and of hypofunctioning P2X7 variants in particular with impaired
glucose homeostasis in both mice and humans.
Hyperglycemia disproportionately affecting African Americans (AA) may
have a genetic basis. We used meta-analyses (m-a) of genome-wide (g-w)
association studies (GWAS) of FG in AA to test whether FG loci identified in
Europeans (EU) also are associated in AA, and to find new AA FG loci.
We performed FG GWAS in 16 cohorts of 20,209 non-diabetic AA (mean
age 56 yr) using additive genetic models to test associations of FG with 3.3M
single nucleotide polymorphisms (SNPs) and combined results in METAL using
inverse-variance weighted m-a. To leverage possible AA-EU heterogeneity
at each SNP, we combined AA METAL results with MAGIC published results
(Manning 2012, PMID 22581228, N=96,496 EU in 29 cohorts) and m-a the
two results files using MANTRA, a Bayesian method accounting for allelic
heterogeneity among population clusters that returns a Bayes Factor, with
(logBF) &gt 6 suggesting g-w SNP-FG association. We evaluated associations
for 23 known FG loci by testing reported Index SNPs (Dupuis 2010, PMID
20081858, Manning 2012) and also finding the Best SNP within +/- 250 kb
of the Index SNP. We sought new loci for replication based on low METAL P
values in AA and high MANTRA logBF in AA plus EU.
For 23 known FG loci, 1 Index (MTNR1B) and 1 Best SNP (GCK) were g-w
significant (P &lt 2.5x10-8) in AA and 8 Index and 23 Best SNPs were nominally
significant (P &lt 0.05). At 10/23 loci the r2 for Index vs. Best SNP was &lt 0.2.
Seven AA loci had a SNP P &lt 10-6 and logBF &gt 6 and 7 more had a SNP P
&lt 10-5 and logBF &gt 4, giving 14 high-interest SNPs to test for replication.
All 23 FG loci known in EU show at least nominal association in AA,
suggesting some genetic determinants of FG are likely similar across AA and
EU, but with allelic heterogeneity at many FG loci. Combining fixed effects m-a
in an AA sample with trans-ethnic m-a in an AA-EU sample has identified a
wealth of interesting new AA FG SNPs to test for replication.
Supported by: NIDDK (DK076); NIH (T32DK007260)
Supported by: R01DK078616; K24DK080140
121-LB
123-LB
Smoking-Genotype Interaction in Type 2 Diabetes Risk: The FramingВ­
ham Heart Study
Using the “Gene Mine” to Identify Novel Diabetes-Susceptibility Loci
JASON L. VASSY, CHING-TI LIU, DENIS RYBIN, JOSÉE DUPUIS, JAMES B. MEIGS,
Boston, MA
SOF ANDRIKOPOULOS, SALVATORE MANGIAFICO, GRANT MORAHAN,
Heidelberg Victoria, Australia, Perth, Australia
Smoking is an important behavioral risk factor for type 2 diabetes (T2D),
but not all smokers get T2D. Small studies have reported certain genesmoking interactions that modify T2D risk. We performed a genomewide-byenvironment interaction study (GEWIS) in the Framingham Heart Study (FHS), a
community-based cohort study, to test whether smoking interacts with genetics
to influence T2D risk and to identify genetic loci where such interaction occurs.
We defined incident T2D as a fasting plasma glucose ≥7.0 mmol/L or use of
diabetes medications and excluded T2D at baseline. We categorized baseline
smoking status as never, current, or former based on validated self-report.
Blood samples were genotyped on the Illumina CARe 50K iSelect chip. We
performed a GEWIS across all single-nucleotide polymorphisms (SNPs) using
Cox regression accounting for relatedness, modeling hazard of incident T2D
as a function of age, sex, 4 principal components, smoking category, SNP,
and smoking*SNP interaction. We used a joint test of (SNP + SNP*smoking)
to test the hypothesis that genotype itself or its interaction with smoking
increases risk for T2D, with p<2*10-5 defining statistical significance for the
joint test. Among 2,987 individuals, 1,024, 842, and 1,121 were never, current,
and former smokers, respectively. Over 2 to 24 years, there were 431 cases
of incident T2D. No SNP met significance for SNP*smoking interaction, but
The Collaborative Cross is a next-generation genetic resource, developed
to simplify discovery of genes controlling complex genetic traits. It consists
of hundreds of inbred mouse strains descended from eight genetically diverse
founders. To identify genetic loci associated with Type 2 diabetes susceptibility,
we characterised basal blood glucose levels and insulin sensitivity using an
insulin tolerance test (0.75IU/kg) in 50 Collaborative Cross strains followed
by genetic linkage analysis using HAPPY modified for the Collaborative Cross.
Strains with a high basal blood glucose level (above 20 mM) and thus strong
genetic predisposition to ОІ-cell dysfunction were further characterised using
intravenous and oral glucose tolerance tests (IVGTT 1g/kg and OGTT 2g/kg).
Linkage analysis localised several hotspots for diabetes susceptibility with
90% confidence. One locus was mapped to chromosome 8 with genomewide significance at 95% confidence (F statistic p<0.05). Glucose tolerance
tests in those with the high basal blood glucose showed several strains had
abnormal glucose tolerance. Two of these strains provide novel mouse models
of Type 2 Diabetes susceptibility with reduced insulin secretion. Our results
validate the utility of the Collaborative Cross as a powerful genetic resource
for the identification of diabetes susceptibility loci and for the generation and
characterisation of novel mouse models for the study of Type 2 Diabetes.
For author disclosure information, see page LB66.
ADA-Funded Research
LB33
Immunology/Transplantation
Immunology
126-LB
Resolution of Autoimmune Diabetes Mellitus Precipitated by Interferon
Therapy for Chronic Hepatitis C
124-LB
JENNIFER Y. HAN, STEPHANIE SMOOKE PRAW, Santa Monica, CA, Los Angeles,
CA
Loss of a Novel Immune Regulatory Pathway in Type 1 Diabetes
MYRIAM CHIMEN, HELEN M. MCGETTRICK, CLARA M. YATES, AMY KENNEDY,
ASHLEY MARTIN, FRANCESCA BARONE, LUCY WALKER, CHRISTOPHER
D. BUCKLEY, GERARD NASH, GEORGE E. RAINGER, PARTH NARENDRAN,
Birmingham, United Kingdom
Interferon (IFN) is a commonly used agent for chronic hepatitis C and is a rare
cause of latent autoimmune diabetes in adults (LADA). LADA is characterized
by circulating autoantibodies against pancreatic beta cell antigens (islet-cell
antibodies [ICA] or glutamic acid decarboxylase antibody[GAD-65 Ab]). The
infrequency with which LADA is encountered and the variability of onset can
present a diagnostic challenge. In addition, the disease course is not welldescribed in patients taking interferon. We present a unique case of interferonassociated LADA which resolved after interferon cessation.
A 68-year-old male was evaluated for acute onset of hyperglycemia of
473mg/dl, 7 months after initiating ribavirin and interferon-alpha (IFN-О±) for
hepatitis C. Anion gap was absent, serum and urine ketones were negative.
Hemoglobin A1C (HBA1C) was 7.2% at diagnosis of diabetes.
After a trial of oral medications including Metformin, the patient was
referred to endocrinology for persistently elevated blood glucose. GAD-65 Ab
was elevated at 17,818U/ml (normal<.5). Insulin was initiated and the patient’s
A1c improved. IFN was discontinued after an extended 72-week course. GAD65 Ab was 10,595, 3041, and 2024U/ml at 1, 4, and 11 months post-therapy
respectively. The patient was weaned off insulin 4 months after completion of
IFN with a HBA1C of 5.2%. Two years later, he remains euglycemic IFN-О± has
antiviral, antiproliferative, and immunomodulatory effects and its use has been
associated with autoimmune diseases such as multiple sclerosis, systemic
lupus erythematosis, thyroid disease, and Type 1 diabetes (T1D Subjects with
IFN-associated diabetes have higher levels of C-peptide and GAD-65 Ab than
T1D. The onset of diabetes ranges from 2-13 months from initiation of IFN to
4 months after therapy completion. Once diagnosed, insulin is often necessary
to achieve glycemic control.
This is the only reported case of resolution of hyperglycemia following the
cessation of IFN therapy.
In type 1 diabetes (T1D), recruitment of T cells to the pancreatic islets
contributes to the destruction of insulin secreting beta cells. Very little is
known about the mechanisms by which T cell migration is regulated during
inflammation, and it is thus difficult to target this aspect of pathology for the
development of therapies. We tested the hypothesis that adiponectin, an antiinflammatory adipose tissue derived cytokine, regulates T cell migration.
In vitro, videomicroscopy was used to assess the migration of lymphocytes
isolated from healthy donors or patients with T1D across TNF-О±/IFN-Оі activated
endothelial cells (EC). In vivo, lymphocyte migration was assessed in a model
of zymosan driven peritoneal inflammation. Adiponectin receptors expression
was measured by flow cytometry.
We observed that migration of human lymphocytes was dose-dependently
blocked by adiponectin (EC50=37nM). This effect was lost when B cells
were absent, but could be regained by the addition of supernatants from
adiponectin stimulated B cells. Mass spectrometry analysis identified the
adiponectin-induced B cell-derived peptide, subsequently named PEPITEM
(PEPtide Inhibitor of Trans-Endothelial Migration). Interestingly, PEPITEM did
not act directly on T cells; rather it stimulated EC to release the lipid mediator
sphingosine 1 phosphate, which in turn inhibited T cell migration. Synthetic
PEPITEM could also effectively inhibit T cell migration in vitro (EC50=19pM). In
zymosan induced peritonitis, T cell recruitment was significantly increased in
mice lacking B cells when compared to wild type animals. This excess of T cell
recruitment was ameliorated by treatment with PEPITEM in vivo.
Lymphocytes isolated from patients with T1D expressed lower levels
of adiponectin receptors, and were released from the inhibitory effects of
adiponectin on transmigration. The addition of PEPITEM to T1D lymphocytes
re-established the block on transmigration. We hypothesise that modulating
the PEPITEM pathway has therapeutic potential for T1D.
127-LB
NCoR KO Reprograms Macrophage Lipid Metabolism Increasing П‰3
Fatty Acid Synthesis and Insulin Sensitivity
Supported by: Diabetes UK; University of Birmingham
PINGPING LI, NATHANAEL J. SPANN, MIN LU, DAYOUNG OH, GAUTAM
BANDYOPADHYAY, SASWATA TALUKDAR, JIANFENG XU, WILLIAM S. LAGAKOS,
DAVID PATSOURIS, AARON ARMANDO, OSWALD QUEHENBERGER, EDWARD
DENNIS, STEVEN M. WATKINS, JOHAN AUWERX, CHIRSTOPHER GLASS,
JERROLD M. OLEFSKY, San Diego, CA, Emeryville, CA, Lausanne, Switzerland, La
Jolla, CA
125-LB
Withdrawn
Macrophage-mediated inflammation is a major contributor to obesityassociated insulin resistance. The co-repressor NCoR inhibits inflammatory
pathway activation in macrophages, and one would predict that removal
of this co-repressor should lead to activation of inflammatory responses.
Surprisingly, we find that macrophage-specific deletion of NCoR leads to an
anti-inflammatory phenotype causing robust systemic insulin sensitization in
obese mice. We traced this mechanism of the paradoxical effect to the ability
of NCoR to co-repress the nuclear receptor LXR. NCoR deletion led to LXR derepression with activation of its downstream transcriptional targets, including
lipogenic pathway genes. These lipogenic genes promote the biosynthesis of
omega-3 fatty acids which produce strong, local, anti-inflammatory insulin
sensitizing effects. Thus, macrophage NCoR deletion leads to reprogramming
of macrophage lipid metabolism, turning these cells into local factories for
the production of omega-3 fatty acids. Therapeutic methods to harness this
mechanism could lead to a new approach to insulin sensitizing therapies.
128-LB
Augmentation of Leptin Receptor Signaling by Loss of Socs3 Induces
Development of Gastric Tumors in Mice
KYOKO INAGAKI-OHARA, SEIYA KATO, TAEKO DOHI, GORO MATSUZAKI,
YASUHIKO MINOKOSHI, AKIHIKO YOSHIMURA, Chiba, Japan, Okinawa, Japan,
Aichi, Japan, Tokyo, Japan
It is well known that leptin derived from adipose tissue acts on its receptor
(ObR) in the hypothalamus to inhibit food intake and energy expenditure.
Leptin and ObR are also expressed in the gastrointestinal tract; however, the
physiological significance of leptin signaling in the gut remains uncertain.
Suppressor of cytokine signaling 3 (SOCS3) is a key negative feedback
regulator of ObR-mediated signaling in the hypothalamus. We now show
that gastrointestinal epithelial cell-specific SOCS3 conditional knockout (T3bSOCS3 ckO) mice developed gastric tumors by enhancing leptin production and
the ObRb/signal transducer and activator of transcription 3 (STAT3) signaling
For author disclosure information, see page LB66.
ADA-Funded Research
LB34
Immunology/Transplantation
pathway. All T3b-SOCS3 cKO mice developed tumors in the stomach but not
in the bowels by 2 months of age, even though the SOCS3 deletion occurred
in both the epithelium of stomach and bowels. The tumors developed in the
absence of the inflammatory response and all cKO mice died within 6 months.
These tumors displayed pathology and molecular alterations, such as an
increase in MUC2 (Mucin 2) and TFF3 (trefoil factor 3), resembling human
intestinal-type gastric tumors. Administration of anti-leptin antibody to T3bSOCS3 cKO mice reduced hyperplasia of gastric mucosa, which is the step
of the initiation of gastric tumor. These data suggest that SOCS3 is an antigastric tumor gene that suppresses leptin overexpression and ObRb/STAT3
hyperactivation, supporting the hypothesis that the leptin/ObRb/STAT3 axis
accelerates tumorigenesis and that it may represent a new therapeutic target
for the treatment of gastric cancer.
After stable hyperglycemia was achieved, all rats were inoculated i.p. with 1
Г— 108 CFU S. aureus. After 2 hours, 20 rats (10 streptozocin-treated, 10 sham)
were euthanized and subjected to peritoneal wash. Ten of the remaining 20
hyperglycemic rats were then rescued with insulin (NPH). These 20 rats were
euthanized at 24 hours and subjected to peritoneal wash. The peritoneal
concentration of the classical/lectin cascade component C4 and the central
complement cascade component C3 were both increased in euglycemic rats
at 2 hours as well as in the insulin-rescued rats at 24 hours compared to
hyperglycemic rats. Peritoneal concentrations of the anaphylatoxin C5a was
> 2-fold higher for insulin-rescued rats compared with hyperglycemic rats.
These findings correlated inversely with colony counts of S. aureus recovered
from the peritoneum. Thus, there were decreased bacteria in euglycemic and
insulin-rescued rats compared to hyperglycemic rats.
Supported by: JSPS
131-LB
129-LB
Hyperglycemia and Associated Findings in Autologous HCT RecipiВ­
ents
Elevated Frequencies of Th22 Cells in Peripheral Blood from Obesity
and Type 2 Diabetes Patients Correlate With Insulin Resistance and
Islets ОІ-Cell Function Loss
MARILYN J. HAMMER, GAIL D’ERAMO MELKUS, M. TISH KNOBF, New York, NY,
New Haven, CT
Independent of history of diabetes, patients with cancer are at an
increased risk for hyperglycemic events due to the malignancy, treatments,
nutritional alterations, physical inactivity, and stress. Hyperglycemia promotes
proinflammatory cytokine, chemokine, and prostaglandin expression. This
inflammatory response further impairs an already compromised immune
system, leading to increased risk for microorganismal invasion and related
adverse outcomes. To better understand associations between hyperglycemia
and its contributors, immune status, and presence of microorganisms in
patients with cancer, we prospectively investigated patients with hematological
malignancies who received autologous hematopoietic cell transplantation
(HCT). Daily morning fasting blood glucose (BG) and leukocytes, documented
microorganisms, and patient demographics in 45 autologous HCT recipients
were collected. In this initial study phase, we used descriptive statistics
and Pearson correlations to evaluate associations between patient factors,
leukocytes, and presence of microorganisms. A total of 1,024 BG and WBC/
ANC values among 27 female and 18 male adult/older adult patients were
analyzed. The mean age was 56 years among an ethnically diverse patient
population. The mean Body Mass Index (BMI) was 28.1.Microorganism
growth occurred in 27 patients, 9 with multiple microorganisms. Coagulasenegative staphylococci (N = 14) and Clostridium difficile (N = 10) were the
most prevalent. Pearson correlations of interest included BG and leukocytes (r
= -.142; p < .0001), mean BG and presence of microorganism (r = .078, p = .014),
age and BMI (r = .138, p < .0001), and BMI and presence of microorganism
(r = .229, p <.0001). In summary, associations were found between BG, age,
leukocytes, BMI, and presence of microorganisms among autologous HCT
recipients. Further investigation and intervention studies are warranted.
RUXING ZHAO, LI CHEN, Jinan, China
The chronic low-grade inflammation has long been recognized as the central
link between obesity associated insulin resistance and type 2 diabetes. In light
of the role of Th22 cells in the pathogenesis of chronic inflammation, we first
identified increased frequencies of Th22 cells in peripheral blood from patients
with obesity and type 2 diabetes. Consistently, we detected elevated IL-22
levels in plasma and increased gene expressions of Th22 specific transcription
factor in peripheral blood mononuclear cells from patients. Moreover, the
remarkable positive correlation of Th22 frequency with both homeostatic
model assessment-insulin resistance index and residual islets ОІ-cell function
indicates that the expansion and hyperactivity of Th22 cells might have
important role in the development of obesity associated insulin resistance and
disease progression to type 2 diabetes.
Supported by: NIH/NINR (K23NR012467)
132-LB
Positivity for Islet Cell Autoantibodies in Subjects With Monogenic
Diabetes Is Associated With Later Diabetes Onset and Higher Hba1c
Level
JANA URBANOVГЃ, BLANKA RYPACKOVA, ZDENKA PROCHAZKOVA, PETR
KUCERA, MARIE CERNA, MICHAL ANDEL, PETR HENEBERG, Prague, Czech
Republic
Islet cell autoantibodies (iAbs) are associated with the autoimmune insulitis,
and belong to the main diagnostic criteria of type one diabetes mellitus
(T1DM). Nevertheless, growing evidence suggests the iAbs presence also in
other diabetes types, surprisingly, in MODY (Maturity Onset Diabetes of the
Young).
The aim of the study was to characterize the cohort of Czech MODY patients
positive for iAbs.
Autoantibodies against glutamic acid decarboxylase 65 (GADA) and protein
tyrosine phosphatase IA-2 (IA2A) were analyzed in a cohort of 31 Czech
MODY subjects, all confirmed by genetic testing. Selected clinical data were
correlated to the iAbs status and kinetics.
Almost one quarter of the MODY subjects examined (7/31; 22.6%) was
positive for iAbs. GADA were more prevalent (7/7) over IA2A (1/7). The iAbs
incidence did not correlate with the HLA risk of T1DM. The iAbs-positive
subjects manifested diabetes significantly later than the iAbs-negative ones,
but displayed worse diabetes control (significantly higher HbA1c level).
Secretion of iAbs decreased with any improvement of diabetes compensation.
Only one of the examined subjects did not correspond to the above and
displayed combined MODY and T1DM signs.
The data suggest transient but highly prevalent iAbs expression in Czech
MODY subjects. The iAbs were found in subjects with rather delayed diabetes
Supported by: Shandong University
130-LB
Hyperglycemia Inhibits Complement-Mediated Immunological Control
of S. Aureus in a Rat Model of Peritonitis
KENJI M. CUNNION, CLIFFORD MAURIELLO, PAMELA HAIR, REUBEN ROHN,
Norfolk, VA
Previous work in our laboratory demonstrated that elevated glucose levels
(> 10 mM) dramatically inhibited complement-mediated immune effectors
critical for control of S. aureus infection. In vitro, high-glucose levels
inhibited opsonization of S. aureus with C3b/iC3b as well as generation of
the anaphylatoxin toxin C5a. Thus, complement defenses were inhibited,
which correlated with increased bacterial survival of neutrophil-mediated
killing. These findings suggested that high-glucose inhibition of complement
effectors against S. aureus may contribute to an increased risk of and severity
of infections caused by S. aureus for patients with diabetes. We now report
preliminary data testing whether hyperglycemia would inhibit complementmediated control of S. aureus infection in a rat peritonitis model. Thirty rats
were treated with streptozocin to induce diabetes and 10 were sham treated.
For author disclosure information, see page LB66.
ADA-Funded Research
LB35
Immunology/Transplantation
Transplantation
manifestation, and in times of insufficient diabetes control. Since improving
of diabetes compensation was associated with decrease of iAbs levels, their
presence may reflect the kinetics of beta-cell destruction induced by other than
autoimmune causes.
135-LB
Beta Cell-Targeted PDL1-CTLA4Ig Over-Expression Protects Allogeneic
Islets from Acute Rejection
Supported by: UNCE 204015, PRVOUK P31/2012, P301/12/1686
MOUSTAFA EL KHATIB, TOSHIE SAKUMA, JASON TONNE, YOGISH KUDVA,
YASUHIRO IKEDA, Rochester, MN
133-LB
Amelioration of Type 1 Diabetes in NOD Mice by Allogeneic Newborn
Blood Transfer Is Associated With Restoration of Self-Tolerance
Islet transplantation has the potential to cure type 1 diabetes mellitus (T1D)
and a subset of type 2 diabetes. Major barrier for wide-spread use of islet
transplant is the requirement of long term immunosuppressive treatment.
Programmed death 1 (PD1) and its ligand, PDL 1, supply inhibitory signals
during T cell activation. CTLA4Ig (Cytotoxic T lymphocyte Associated antigen
4 IgG) has been used as an inhibitor of T cell co-stimulation. In this study, we
determined the influence of beta cell-targeted over-expression of PDL1 and
CTLA4Ig on T1D development and allo-islet rejection. We employed adenoassociated virus 8 (AAV8) vectors with a mouse insulin 2 promoter to achieve
beta cell-specific expression of an artificial PDL1-CTLA4Ig poly-protein. Beta
cell-targeted overexpression of PDL1-CTLA4Ig protected non-obese diabetic
mice (NOD) from developing hyperglycemia. Immuno-histology revealed the
suppression of autoimmunity-mediated insulitis in PDL1-CTLA4Ig expressing
islets. We then analyzed the effects of PDL1-CTLA4Ig expression on rejection of
allo-islets in MHC-matched recipient mice. Streptozocin (STZ)-induced diabetic
DBA2 mice received allo-islets, isolated from BALB/c mice with or without
pretreatment of the PDL1-CTLA4Ig-expressing vector. As a positive control, we
also transplanted alginate-encapsulated allo-islets into diabetic DBA mice.
Although untreated islets were rejected within 10 days, mice transplanted
with the PDL1-CTLA4Ig-expressing islets remained normoglycemic for at least
40 days. Encapsulation of islets delayed immune-rejection for 3 weeks after
transplant. The present study demonstrated the utility of the beta cell-targeted
AAV8 vector system and the potent immune-suppressive effects of beta
cell-targeted PDL1-CTLA4Ig overexpression against autoimmunity and acute
graft rejection. Beta cell-targeted PDL1-CTLA4Ig expression can provide an
alternative strategy for immunosuppression-free islet transplantation.
SUNDARARAJAN JAYARAMAN, MARK HOLTERMAN, BELLUR PRABHAKAR,
Chicago, IL, Peoria, IL
We have previously shown that a single injection of allogeneic newborn
blood, functionally equivalent to umbilical cord blood, into un-preconditioned
prediabetic NOD mice prevented the onset of type 1 diabetes, which was
accompanied by transient chimerism and alteration of gene expression in
T-cells (Jayaraman et al. 2010; J. Immunol. 184:3008-15). We now show that
allogeneic newborn blood transfer results in the elimination of diabetescausing potential of T lymphocytes. Global unresponsiveness, predominant
under diabetic condition was substantially reduced whereas alloantigen
driven T-cell proliferation was enhanced in mice cured of diabetes. Protection
against diabetes did not accompany altered frequency of CD4+ cells expressing
CD62L, CD44 or FoxP3. Both the ability of CD4+CD25+FoxP3+ T regulatory
cells to exert suppression and the sensitivity of CD4+CD25- T effector cells
to T regulatory cell mediated suppression were similar in diabetic and cured
mice. Gene expression analysis of splenocytes derived from cured mice using
qRT-PCR revealed the repression of pro-inflammatory genes such as Cela3b
and enhancement of Mif, respectively implicated in diabetes manifestation
and protection by our recent transcriptome analysis (Jayaraman et al. 2013;
PloS One, 8: e55074). Importantly, activation induced T-cell death, crucial for
maintaining peripheral tolerance, was substantially enhanced in CD4+ T-cells
derived from cured mice. Taken together, these data indicate that allogeneic
newborn blood transfer affords protection against type 1 diabetes by restoring
self-tolerance and modifying gene expression.
Supported by: Mayo Foundation
134-LB
136-LB
MIF Contributes to the Inflammatory Process in Type 1 Diabetes by
Mediating Macrophages and Dendritic Cells Maturation
The Potential Contribution of Beta-Cell Purinergic Signaling and
Ectonucleotidases in the Pathophysiology of Diabetes: Preliminary
Rodent Study
ALONSO VILCHES-FLORES, YURIKO ITZEL SANCHEZ-ZAMORA, MIRIAM RODRIGUEZSOSA, Tlalnepantla, Mexico
Type 1 diabetes (T1D) is characterized by a cellular infiltrate in pancreatic
islets where ОІ cells are destroyed. The recognition of antigens and auto
antigens takes place by macrophages (Mo) and dendritic cells (DCs). Previously
we have showed that Macrophage migration inhibitory factor (MIF) induces
the expression of co-stimulatory molecules on Mo and DCs on infection
diseases. However, the role of MIF on Mo and CDs has not been explored in
T1D. Here, we determined the expression of co-stimulatory molecules on Mo
and DCs from WT and MIF-/- mice with experimental T1D induced by STZ.
Cells extracted from pancreas and spleen were treated in vitro with antibodies
anti- CD80, CD86, CD40, MHC-II, TLRs and CD4+CD25+FOXp3+ cells. MIF-/mice did not increase high glucose levels compared with WT mice after STZ.
Pro-inflammatory cytokines presence in serum was diminished in MIF-/-STZ
mice, but the anti-inflammatory cytokines was higher than WT STZ mice during
all the experiment. These suggest the absence of MIF prevents an exacerbated
inflammatory response, which correlates with blood glucose levels. Moreover,
MIF-/-STZ mice had less expression of CD80, CD86, MHCII, TLR-2 and TLR4 either in spleen or pancreatic islets Mo and CDs. In addition, CD4+CD25+
spleen cells from healthy MIF-/- mice increased FOXp3 transcription factor
expression regarding WT mice. Eight weeks after of T1D induction FOXp3
expression was higher in MIF-/- mice than WT mice. Our results suggest MIF
favors the expression of co-stimulatory molecules in the Mo and CDs in T1D.
Additionally we propose that MIF down-regulate the proliferation of regulatory
T cells and MIF targeted therapy, combined with existing can help to decrease
T1D course.
CARMEN FOTINO, R. DAMARIS MOLANO, OLIVER UMLAND, ANDREA VERGANI,
FABIO GRASSI, RODOLFO ALEJANDRO, CAMILLO RICORDI, PAOLO FIORINA,
ANTONELLO PILEGGI, Miami, FL, Boston, MA, Bellinzona, Switzerland
Extracellular ATP is regulated by purinergic signaling and ectonucleotidases
(ENTPDases), and may amplify ОІ-cells inflammation during autoimmunity
and islet rejection. We evaluated P2X7R and ENTPDases (CD39 and CD73)
expression in mouse islets and pancreas.
Viable ОІ-cells (R2D6+) in islets exposed to 24hr stress were 45.5% in
control, 65.7% in IFN-Оі, 66.6% in cytokines, and 61.3% in high glucose. P2X7R,
E-NTPDases and MHC-I expression is shown in Table 1.
In dissociated pancreas of C57BL/6, prediabetic NOD (pNOD) and NOD.SCID
mice ОІ-cells were 80%, 29.9% and 30.2%. R2D6+P2X7R+ cells were 71.5%,
26.2%, and 74%. R2D6+CD39+ cells were 8.5%, 46%, and 26%. R2D6+CD73+
cells were, 8.2%, 5.7% and 26.6%. CD3+ cells were 10.9%, 15.3% and 0%.
CD3+P2X7R+ cells were 11.7% in pNOD and 6.1% in C57BL/6. CD3+CD39+ cells
were 23.6% in pNOD and 3.3% in C57BL/6, and CD3+CD73+ similar (55.4% and
66%, respectively). P2X7R expression by CD31+ endothelial cells was similar in
C57BL/6 and NOD.SCID (62.1% and 62.4%), and 30.5% in pNOD; CD39+ was
similar in all strains (40.1%, 42.5%, and 51.8%, respectively). CD31+CD73+ cells
were 13.8% in NOD.SCID, 4.8% in pNOD and 5.3% in C57BL/6.
P2X7R and E-NTPDases expression increase in ОІ-cells after stress. In pNOD
P2X7R and CD39 are low and high in ОІ-cells; both increase in CD3+ cells. ATP/
P2X and E-NTPDases may contribute to islet immunity. Their modulation could
be appealing to preserve ОІ-cells in diabetes.
Supported by: CONACYT (152224); UNAM-DGAPA-PAPIIT (IN212412); Miguel
Aleman Foundation
Supported by: DRIF
For author disclosure information, see page LB66.
ADA-Funded Research
LB36
Insulin Action/Molecular Metabolism
Insulin Action—Adipocyte Biology
Insulin Action—Glucose Transport and
Insulin Resistance in Vitro
137-LB
139-LB
AKT2 Is Not Required for Insulin Regulation of Lipolysis In Vivo
SHLOMIT KOREN, QINGWEI CHU, BOB MONKS, LISA M. DIPILATO, MATT
EMMETT, MORRIS J. BIRNBAUM, Philadelphia, PA
Physiological Hemodynamics and Transport Restore Insulin and
GlucaВ­gon Responses in a Normal Glucose Milieu in Hepatocytes In
Vitro
Regulation of lipolysis is under tight hormonal control mainly by
catecholamines and insulin. The general consensus is that insulin antagonizes
catecholamine-activated lipolysis through Akt phosphorylation and activation
of PDE3B. Recently, this hypothesis was challenged as in vitro studies
demonstrate that insulin suppresses lipolysis by an Akt- independent pathway.
To address this question in vivo, we studied lipolysis in mice deficient for AKT2,
the major isoform expressed in adipocytes. We found that AKT2 whole-body
knock out (KO) mice have mildly reduced adiposity and comparable levels of
adipokines compared to wild type (WT) mice. In the fed state and following
an oral glucose challenge, AKT2 KO mice are glucose intolerant and display
hyperinsulinemia; however exhibit normal insulin mediated suppression of
lipolysis. Furthermore, insulin significantly inhibits lipolysis in both genotypes
during insulin tolerance test (ITT) and hyperinsulinemic euglycemic clamp
(attached figure) in the presence of equivalent insulin levels. Insulin inhibits
catecholamine-induced lipolysis in primary differentiated brown fat adipocytes
(BFA) of AKT2 KO to a similar extent as in BFA from WT mice. These results
suggest that while AKT2 is an important component of insulin signaling in
glucose metabolism it is not required for insulin regulation of lipolysis in vivo.
The existence of multiple pathways by which insulin regulates metabolism and
adipose tissue may lead to more targeted therapeutics.
AJIT DASH, TYE DEERING, SVETLANA MARUKIAN, JOSHUA THOMAS, BRIAN
WAMHOFF, BRETT BLACKMAN, Charlottesville, VA
The use of primary hepatocytes as an in vitro tool for drug discovery and
development in diabetes research is severely limited by their lack of insulin
sensitivity. Routine culture conditions for hepatocyte survival in vitro mandate
super-physiological levels of insulin and glucose in media, confounding their
applicability and relevance. We previously described a system that applies
physiological hemodynamics and transport to restore and retain hepatocyte
phenotype, resulting in drug and hormone responses at in vivo levels. We
cultured rat and human hepatocytes in this system at physiological insulin and
glucose levels before testing them for insulin/glucagon responsiveness. The
regulation of gluconeogenesis was tested by addition of substrates lactate/
pyruvate or glycerol in the presence of glucagon or insulin, and measuring
glucose in supernatants. Glucagon increased glucose output by 50-80% while
insulin was seen to inhibit it by 25-40%. Hepatocytes were then cultured in the
presence of high or low glucose/insulin levels for 7 days. Lipid accumulation
(nile red stain), total triglycerides and metabolic activity (p450 glo assays)
were assessed. High glucose/insulin levels resulted in a steatotic state
characterized by lipid accumulation and increased triglycerides (3 fold) along
with a reduction of CYP3A2 and CYP1A1 activity (3- 6 fold) relative to low
glucose/insulin conditions. These changes were prevented by concomitant
administration of pioglitazone (1.5ОјM). In conclusion, we demonstrate a novel
liver platform that maintains hepatocytes at physiological glucose and insulin
levels retaining their responsiveness to insulin and glucagon. A high glucose/
insulin insulin environment in the system induces steatotic changes along with
metabolic suppression similar to clinical non alcoholic fatty liver disease, which
are preventable by administration of Pioglitazone at plasma Cmax levels.
Insulin Action—Signal Transduction,
Insulin, and Other Hormones
140-LB
LRP6 Mutation Alters Expressions of Insulin and IGF Receptor and
Causes Insulin Resistance in Humans
RAJVIR SINGH, RENATA BELFORT DE AGUIAR, SARITA NAIK, SHEIDA MANI,
KAMAL OSTADSHARIF, DETLEF WENCKER, MASOUD SOTOUDEH, REZA
MALEKZADEH, ROBERT S. SHERWIN, ARYA MANI, New Haven, CT, Isfahan,
Islamic Republic of Iran, Hartford, CT, Tehran, Islamic Republic of Iran
Insulin Action—Cellular and Molecular
Metabolism
We have identified a large kindred in whom a non-conservative mutation
(R611C) in the Wnt co-receptor LRP6 underlies the development of autosomal
dominant early onset CAD, type 2 diabetes and metabolic syndrome. Healthy
nondiabetic LRP6 mutation carriers exhibited insulin resistance compared to
noncarrier relatives during oral glucose tolerance test. The skeletal muscle
biopsies and skin fibroblasts of the mutation carriers showed diminished
TCF7L2-dependent transcription of insulin receptor and decline in insulin
signaling activity. Further investigations showed that LRP6 mutation increases
phosphorylation of multiple serine residues of the IRS-1 in LRP6R611C
fibroblasts, which was accounted for by enhanced activation of mTORC1.
Increased mTORC1 activity correlated with higher IGFR expression and
subsequent activation of ERK1/ERK2 in LRP6R611C compared to wildtype
fibroblasts. Further investigations revealed posttranscriptional regulation
of IGFR by LRP6. In IGF-1 treated LRP6 knockdown cells IGFR was stabilized
by sumoylation. These findings identify the Wnt/LRP6/TCF7L2 axis as a
regulator of glucose metabolism and a potential therapeutic target for insulin
resistance.
138-LB
Amyloid ОІ42 Administration Impairs Energy Metabolism In Vivo and In
Vitro
JULIANE K. CZECZOR, TIM CONNOR, AMANDA J. GENDERS, KEN WALDER,
SEAN MCGEE, Waurn Ponds, Australia
Amyloid β42 (Aβ42) is a protein implicated in Alzheimer’s Disease (AD), in part
through causing impaired neuronal metabolism. Obese and diabetic patients
have increased circulating AОІ42, yet it is unknown whether circulating AОІ42
contributes to altered metabolism in these conditions. The aim of this study
was to determine whether AОІ42 alters metabolism of insulin sensitive cells in
vitro, and whole body metabolism in vivo. Monomeric AОІ42 (mAОІ42) increased
glucose production in FAO hepatocytes, while aggregated AОІ42 (aAОІ42) had no
effect. Similarly, mAОІ42 impaired glucose uptake in 3T3-L1 adipocytes, while
aAОІ42 had no effect. We next investigated the effect of mAОІ42 or scrambled
AОІ42 (control) administration to mice (1Вµg / day; I.P. injection) over 2 weeks.
Administration of mAОІ42 had no effect on bodyweight or food intake compared
with control mice. However, administration of mAОІ42 reduced oxygen
consumption and total carbohydrate oxidation compared with control animals
(p ≤ 0.05).
This data shows that monomeric AОІ42 impaired glucose metabolism while
aggregated AОІ42 had no effect. This data suggests that not only is AОІ42 involved
in the pathology of AD, but it may also be involved in the dysregulation of
metabolism in obesity and type 2 diabetes, where circulating AОІ42 levels are
elevated.
Supported by: NIH (R01HL094784-01), (R01HL094574-03 to A.M.); NIDDK
(T32DK007058 to R.S.S.)
141-LB
Mechanism of Angiotensin II-Inhibited Insulin Signaling Pathway
EUN KYUNG KOH, HYUN-JU JANG, HAE-SUK KIM, JEONG-A KIM, Birmingham,
AL
It is well recognized that hypertensive individuals have elevated level of
angiotensin II (ANG II). Elevated level of ANG II is known to be related to insulin
resistance in the metabolic and cardiovascular tissue. Mammalian target of
rapamycin (mTOR) is thought to be important in insulin resistance, cardiac and
Supported by: NHMRC
For author disclosure information, see page LB66.
ADA-Funded Research
LB37
Integrated Physiology/Obesity
vascular smooth muscle cell hypertrophy. In the previous study from our lab, we
reported that activation of mTOR/p70S6K by ANG II impairs insulin-stimulated
vasodilation through phosphorylation of IRS-1 at Ser 636/639. In the present
study, we investigated upstream/downstream molecules that are involved in
ANG II-activated mTOR/p70S6K pathway. We treated ANG II (100 nM) on HEK
293 stably transfected with AT1R (HEK 293 AT1a) cells for various time points
(5 min, 10 min, 20 min, 30 min, 40 min, 60 min and 120 min, respectively). We
observed that ANG II stimulated phosphorylation of both mTOR and p70S6K as
early as 5 min and maximally stimulated between 30 min to 60 min. ANG IIstimulated phosphorylation of P70S6K was decreased when the cells were pretreated with wortmannin (PI 3-kinase inhibitor, 100 nM), Diphenyleneiodonium
(NADPH oxidase inhibitor, 10 ВµM) , N-acetyl cysteine (antioxidant, 10 mM),
and losartan (AT1R blocker, 10 ВµM), but not PD98059 (MEK inhibitor, 20 ВµM),
and PD123319 (AT2R blocker, 10 ВµM). This suggests that NADPH oxidase is
involved in ANG II-stimulated mTOR activity. Next, we examined whether PKC
and receptor endocytosis, or SGK (serum glucocorticoid kinase) are involved
in ANG II-stimulated mTOR. ANG II-stimulated phosphorylaion of p70s6K was
decreased when cells were treated with rottlerin (PKCОґ inhibitor, 10 ВµM),
dynasore (endocytosis inhibitor, 80 ВµM) and GSK650394 (SGK inhibitor, 10 ВµM).
Interestingly, ANG II stimulated phosphorylation of PKC Оґ which was inhibited
by SGK inhibitor, GSK 650394. From these results, we conclude that ANGIIstimulated SGK/PKCОґ/NADPH oxidase may play a role in activation of mTOR
which contributes to inhibition of insulin signaling.
N
BMI
AIRarg
AIRarg
MAX
ISR
ICC ICC
AIRarg AIRarg
MAX
(meanВ±SD) Geometric Geometric Geometric
mean
mean
mean
(95% CI) (95% CI) (95% CI)
31.5В±2.8
9.9 a
47.9 a
37.6 a
0.93
(8.8,11.1) (41.9,54.8) (32.5,43.5)
33.0В±2.6
5.9 b
23.6 b
17.6 b
0.92
(5.3,6.5) (21.1,26.5) (15.3,20.2)
8.7 c
4.6 c
0.91
32.8В±3.9
4.0 c
(3.6,4.3) (7.9,9.6) (4.0,5.3)
NGT 23
(12M/11W)
PDM 8
(2M/6W)
T2DM 22
(11M/11W)
ANOVA across
populations (P).
Superscripts that
differ from one
<0.001
another indicate
statistically
separable
parameters, P<0.005.
<0.001
ICC
ISR
0.94
0.87
0.87
0.96
0.79
0.95
<0.001
AIRarg, AIRargMAX, and ISR differ across the 3 populations (all P<0.001).
Overall, AIRs had high R. AIRarg also correlates with AIRargMAX within
each group and across all 3 populations (r=0.98), suggesting that the basal
responses track with glucose-potentiated, both within and across GT. In
conclusion, Arg testing has high repeatability within each GT population and
distinguishes among NGT, PDM, and T2DM, suggesting that it may be useful
to assess changes in BCF over time.
Integrated Physiology—Insulin Secretion
In Vivo
142-LB
Supported by: FNIH Biomarkers Consortium Beta Cell Project
Withdrawn
144-LB
Modeled Response to a Standard Meal Is Useful Method to Characterize
Beta Cell Function (BCF) and Insulin Sensitivity (IS) Across Spectrum
of Glucose Tolerance (GT): Corroboration With FSIGT
DANNY CHEN, CHIARA DALLA MAN, CLAUDIO COBELLI, DAVID A. FRYBURG,
RALPH H. RAYMOND, DOUGLAS S. LEE, RICHARD N. BERGMAN, DARKO
STEFANOVSKI, FOR BETA CELL TEAM OF FNIH BIOMARKERS CONSORTIUM,
Cambridge, MA, Padova, Italy, East Lyme, CT, Skillman, NJ, Los Angeles, CA
It is important to easily measure BCF and IS in longitudinal clinical trials
and show similar responses with methodology like the FSIGT. Mixed meal
tolerance tests (MMTT) are appealing due to simplicity and relevance to enteric
physiology, yet complex due to variable absorption. The goal of this study is
to measure BCF and IS to a standard, commercially available 450 kCal meal
across the spectrum from normal GT (NGT) to prediabetes (PDM) to type 2 DM
(T2DM) and to compare the BCF and IS responses to those from the FSIGT.
All subjects were tested after an overnight fast on 3 separate days. Each subject
had 2 MMTTs and 1 FSIGT. Parameters for BCF were estimated using published
methods. The table summarizes sample size, BMI, and respective MMTT/FSIGT
measures for: IS (Si); insulin release (О¦tot and AIRg); and disposition index (DItot
and DI) by group. MMTT parameters and FSIGT Si summarized as geometric
means (95% CI); all others as arithmetic means (95% CI).
Insulin Sensitivity
143-LB
Arginine (Arg) Stimulation Provides Repeatable Measures of Beta
Cell Function (BCF) that Can Distinguish Across Spectrum of Glucose
Tolerance (GT)
Insulin Secretion
Disposition Index
N
BMI
MMTT Si FSIGT Si MMTT FSIGT AIRg MMTT FSIGT DI
(kg/m2) (10-4/ ((ОјU/ (10-4/ ((ОјU/ml) О¦tot (ОјU min/ DItot
ml)(min))
(min)) (10-9/min) ml) (10-13/ ((ОјU/
ml)(min2))
a
a
a
a
NGT 23 12M/11W) 31.5
4.5
1.6
102.6
914
464 a
1339 a
(30.3-32.7) (3.83-5.33) (1.23-2.08) (89.0-118.4)(594-1235) (375-573) (970-1709)
PDM 8
33.0
2.3 b
1.2 a
108.4 a 412 b
250 a
520 b
(2M/6W)
(31.0-35.0) (1.75-3.04) (0.9-1.59) (93.8-125.3)(91-733) (190-329) (124-915)
T2DM 22
32.8
1c
0.49 b
15.4b
10.4 b
16.8 b
9.3 b
(11M/11W) (31.1-34.5) (0.74-1.35) (0.29-0.8) (12.8-18.6) (-8.7-29.6) (11.3-24.9) (-13.8-32.5)
ANOVA across <0.001
<0.001
<0.001
<0.001 <0.001 <0.001
populations (P)
Superscripts
that differ from
one another
are statistically
separate for
that parameter,
P<0.05.
DAVID A. FRYBURG, R. PAUL ROBERTSON, RALPH H. RAYMOND, DOUGLAS S.
LEE, FOR BETA CELL TEAM OF FNIH BIOMARKERS CONSORTIUM, East Lyme, CT,
Seattle, WA, Skillman, NJ, Cambridge, MA
The ability to reproducibly measure BCF in longitudinal clinical trials is
desirable. Useful BCF methods should distinguish among normal GT (NGT),
prediabetes (PDM), and type 2 DM (T2DM). Acute insulin responses to Arg
under both basal (AIRarg) and glucose-potentiated (AIRargMAX) conditions
measure BCF, but within-subject variability across spectrum of GT has not
been assessed. The objectives of this study are to assess: 1. Response to Arg
in men and women with NGT, PDM, and T2DM; and 2. Repeatability (R) of the
methodology.
During 2 separate visits, subjects received Arg (5 gm IV) after overnight fast.
AIRarg was determined in first 5 min post Arg followed by a 60 min infusion
of glucose and repeat injection of Arg (AIRargMAX). AIRargMAX - AIRarg =
Insulin Secretory Reserve (ISR). All AIR parameters are adjusted for basal
insulin (AIR/[basal insulin] in ОјU/mL). Table includes intraclass correlation
coefficient (ICC), a measure of R. ICC > 0.8 = high R.
For author disclosure information, see page LB66.
ADA-Funded Research
LB38
Integrated Physiology/Obesity
Integrated Physiology—Liver
For MMTT and FSIGT, Si, О¦tot and AIRg, and DI, values decline from NGT
to T2DM (all P<0.001). Correlation analysis for each MTT/FSIGT parameter
pair ACROSS ALL 3 GROUPS: Si (r=0.69); О¦tot/AIRg (r=0.73); and DItot and
DI (r=0.74), suggesting that values from the tests tracked similarly across GT
states. In conclusion, modeled results from the MMTT correspond to FSIGTderived parameters across range of responses of GT spectrum.
147-LB
Identification of Monounsaturated Fatty Acids (MUFA) as Endogenous
FAAH Inhibitors
JIE LIU, RESAT CINAR, YUHONG LIN, KEMING XIONG, JAMES NTAMBI, GEORGE
KUNOS, Rockville, MD, Madison, WI
Supported by: FNIH Biomarkers Consortium Beta Cell Project
High-fat diet induced obesity (DIO) is associated with increased hepatic
expression of lipogenic genes, including stearoyl CoA desaturase-1 (SCD1),
and mice deficient in SCD1 are resistant to DIO. DIO has also been linked to
increased activity of the endocannabinoid/CB1 receptor system, including
increased hepatic levels of the endocannabinoid anandamide (AEA), due to
the reduced activity of the AEA-degrading enzyme, fatty acid amide hydrolase
(FAAH). We have shown endocannabinoids contribute to diet-induced insulin
resistance in mice via hepatic CB1-mediated inhibition of insulin signaling
and clearance. Here we show that hepatic levels of AEA and FAAH activity
remain unaffected by high-fat diet (HFD) in SCD1-/- mice, and that the
monounsaturated fatty acid (MUFA) products of SCD1, palmitoleic acid and
oleic acid, inhibit FAAH activity in vitro with a higher potency as compared with
saturated fatty acids (16:0 and 18:0) and polyunsaturated fatty acid (20:4n6
and 22:6n3). HFD markedly increases hepatic SCD1 activity in wild type mice
as well as in CB1-/- mice with transgenic re-expression of CB1 in hepatocytes
(htgCB1-/-), but not in global CB1 knockout (CB1-/-) mice. Treatment of HFD-fed
mice with the SCD1 inhibitor A939572 prevented the HFD-induced reduction of
hepatic FAAH activity, normalized endogenous AEA level, and improved insulin
sensitivity. SCD1-/- mice on HFD remain insulin sensitive, but develop glucose
intolerance and insulin resistance in response to chronic treatment with the
FAAH inhibitor URB597. We conclude that the MUFA products of SCD1 act as
endogenous FAAH inhibitors. This may account for the HFD-induced increase
in hepatic AEA, which then activates hepatic CB1 receptors to induce hepatic
insulin resistance.
145-LB
Arginine (Arg) Is Preferred to Glucagon (Glgn) in Stimulation Testing
for Beta Cell Function (BCF)
DAVID A. FRYBURG, R. PAUL ROBERTSON, RALPH H. RAYMOND, DOUGLAS S.
LEE, FOR BETA CELL TEAM OF FNIH BIOMARKERS CONSORTIUM, East Lyme, CT,
Seattle, WA, Skillman, NJ, Cambridge, MA
Arg and Glgn have been used as stimuli to quantify acute insulin secretory
responses (AIR). To date no study has compared the responses to Arg and Glgn
nor the repeatability (R) of the tests within the same subjects. The objectives
of this study were to determine: 1. the tolerability of both procedures; and 2.
the repeatability of the BCF measures obtained with Arg and Glgn.
Obese (BMI 31.5В±2.8 (kg/m2)) subjects (n=23 (12M/11W)) with normal
glucose tolerance were studied twice with Arg or Glgn in a randomized crossover. On separate days during each of 2 visits, AIRs to Arg (5 gm IV over 30
sec) and Glgn (1 mg IV over 30 sec) were measured at basal glucose (AIRarg
and AIRglgn) and after 60 min infusion (900 mg/min) of glucose (glucosepotentiated AIRs (AIRargMAX and AIRglgnMAX)). Table summarizes results.
Insulin Secretory Reserve (ISR)= AIRargMAX-AIRarg. R assessed using
intraclass correlation coefficient (ICC); values of ICC > 0.8 = high R.
AIRarg
Insulin (ВµU/mL)
geometric means (95% CI)
ICC
AIRarg ISRarg AIRglgn AIRglgn ISRglgn
MAX
MAX
95
460
361
113
606
465
(85,106) (392,541) (302,431) (101,127) (512,718) (347,624)
0.93
0.92
0.91
0.82
0.75
0.32
Supported by: NIH
148-LB
All subjects had significant responses to Arg and Glgn. Arg yielded better
R than Glgn. AIR to Arg and Glgn correlated with one another across tests
(AIRarg:AIRglgn r= 0.64; AIRargMAX to AIRglgnMAX r=0.84). Most common
adverse events with Arg were mild transient flushing (33%) and oral
paresthesias (46%). For Glgn, nausea was common (43%) and was moderate
in severity in 13%. Due to better repeatability and tolerability with Arg, we
recommend Arg over Glgn as a stimulus for testing BCF.
Ethnic Differences in Circulating Lipoprotein Profiles May Be
Protective Against NASH in African Americans
ANNA GARCIA, JOSEPH ANTOUN, RONALD H. CLEMENTS, BRANDON
WILLIAMS, PAMELA MARKS-SHULMAN, EMILY A. ECKERT, ROBYN A. TAMBOLI,
CHARLES R. FLYNN, NAJI N. ABUMRAD, Nashville, TN
Nonalcoholic fatty liver disease (NAFLD) is a disorder of excessive hepatic
fat (simple steatosis, SS) associated with lipoprotein derangements in a
dose dependent fashion, independent of obesity and insulin resistance. Most
reported studies, however, were performed in Class I-II (BMI: 25-35 kg/m2)
obese, but little is known about such derangements in Class III (BMI: >40)
obesity.
We assessed lipid profiles in 31 Class III Caucasian and African American
subjects scheduled for bariatric surgery. Using NMR spectroscopy, we
determined triglyceride (TG), HDL cholesterol, ApoB100, VLDL, LDL, and
HDL concentrations and respective lipoprotein particle sizes and subclass
concentrations. Subjects were segregated into 3 age-, BMI- and gendermatched cohorts based on NAFLD Activity Scoring (NAS) of liver biopsies
obtained at surgery; this led to classifying subjects as normal (n=11), SS (n=11),
or NASH (n=9). African Americans (n=9) did not display NASH. Insulin clamps
performed in 4 subjects of each group revealed significant decreases (p<0.05)
in hepatic insulin sensitivity in NASH compared to SS. Plasma lipid profiles
revealed that NASH subjects had increased TG (63%), large VLDL concentration
(53%) and size (16%) and lipoprotein insulin resistance scores (LP-IR, 60%).
Compared to Caucasians, African Americans with SS had decreased levels of
total and small, medium and large VLDL, LDL, TG, LP-IR, and ApoB100, and had
increased HDL size (p<0.05). The improved lipid profile in African Americans
may contribute to protection from NASH, suggestive that altered circulating
lipoprotein production or uptake may be indicative of NAFLD progression in
Class III obese insulin resistant Caucasians.
Supported by: FNIH Biomarkers Consortium Beta Cell Project
146-LB
A Broad Range, Highly Sensitive, Small Sample Volume ChemiВ­luminВ­
escent ELISA for Measuring Insulin in Mouse and Rat Models
JULIE RASKU, ELIZABETH WEISS, JULIE MELITO, CHRIS WISHERD, DAVID RICE,
RUSSELL JARRES, CHRISTINE ONTHANK, MARTIN BLANKFARD, Salem, NH
Mouse and rat models are common preclinical models in diabetes research.
Quantification of insulin in serum or plasma over a wide range of disease
states or pre and post drug treatment is vital in furthering diabetes research.
Many commercial rodent insulin ELISAs require extra sample dilution steps to
ensure concentrations fall within a limited standard curve range. This results
in increased sample preparation time as well as potential re-dilution and retesting of samples. The aim of this study was to develop a broad range, highly
sensitive, small volume (<10 ВµL) mouse/rat insulin ELISA to address these
issues. The sandwich assay uses a black 96 well plate. Standards (0.1 -200
ng/mL), samples and controls (5 ВµL ea) were added to the plate followed by
conjugate, incubation, plate wash, chemiluminescent substrate, and reading
after 1 min. Sample concentrations were calculated from the relative light units
which are directly proportional to the amount of insulin in the sample. Analytical
and functional sensitivity were 0.08 ng/mL and 0.10 ng/mL, respectively.
Sample linearity for mouse and rat samples (n=3 ea) across 3 dilutions ranged
from 99-107% with r2 values of 0.997. Samples were spiked with 3 levels of
insulin and recovered at averages of 95, 91, and 97% at the low, mid, and high
spikes, respectively. Serum and plasma concentrations from normal, fasted or
fed diabetic and non-diabetic mice and rats ranged from 0.24 ng/mL to 129.7
ng/mL (n=76). CVs of the sample duplicates were 0.14-12.1% (median 1.7%).
This study demonstrates the accuracy and linearity over the 2000-fold dynamic
range of this chemiluminescent ELISA using a 5 ВµL sample size. The assay
eliminates the need for sample dilution and provides the flexibility to run both
mouse and rat samples on the same plate. Other advantages include a short
2-hour run time, the use of a standard chemiluminescent plate reader and
potential time and cost savings for high volume screening labs.
For author disclosure information, see page LB66.
ADA-Funded Research
LB39
Integrated Physiology/Obesity
149-LB
levels. In addition, we find that exogenous leptin suppresses the refeeding
response only during the daytime, in parallel with increased hypothalamic
pSTAT3 signaling, suggesting leptin sensitivity in the hypothalamus is
regulated in a circadian manner. We further discover that Bmal1 expression in
the hypothalamus is necessary for the circadian control of the acute refeeding
response to fasting in mice, and that genetic ablation of the hypothalamic
clock leads to increased peripheral insulin resistance during hyperinsulinemic
euglycemic clamp. Surprisingly, restriction of feeding to the night reversed
insulin resistance in circadian mutant mice. These results provide genetic
evidence for the regulation of energy and glucose homeostasis by the
hypothalamic clock and have therapeutic implications for circadian intervention
to treat metabolic disorders.
Dietary Iron Regulates the Circadian Rhythm of Hepatic GlucoВ­neoВ­
genesis Through Heme Synthesis
DONALD A. MCCLAIN, CREIGHTON MITCHELL, JINGYU HUANG, JUDITH
SIMCOX, Salt Lake City, UT
The circadian rhythm of the liver is important in the maintenance of glucose
homeostasis, and disruption of this rhythm is associated with type 2 diabetes
risk. Feeding is one factor that sets the circadian clock in peripheral tissues,
but relatively little is known about the role of specific dietary components in
that regard. We have assessed the effects of dietary iron on the circadian
rhythm of the liver. Dietary iron affects circadian glucose metabolism through
heme-mediated regulation of the interaction of Rev-ErbО± with its cosuppressor
NCOR. Loss of regulated heme synthesis was achieved by aminolevulinic acid
(ALA) treatment of mice or cultured cells, to bypass the rate-limiting enzyme in
hepatic heme synthesis, ALAS1. ALA treatment abolishes differences in hepatic
glucose production and in the expression of gluconeogenic enzymes seen
with variation of dietary iron. The differences among diets are also lost with
inhibition of heme synthesis by treatment with isonicotinylhydrazine. Heme
levels respond to dietary iron through modulation of the level of Peroxisome
Proliferator-Activated ReceptorОі Coactivator 1О± (PGC-1О±), a transcriptional
activator of ALAS1. Treatment of mice with the antioxidant n-acetylcysteine
diminished the PGC-1О± variation observed among the iron diets, suggesting
that iron may be acting through reactive oxygen species signaling to regulate
PGC-1О±. Together, these studies show that dietary iron alters the circadian
rhythm of metabolism through control of intracellular heme synthesis.
152-LB
Glycine Sensing in the Dorsal Vagal Complex Lowers Food Intake
JESSICA T. YUE, TONY K.T. LAM, Toronto, ON, Canada
Glycine in the dorsal vagal complex (DVC) activates N-methyl-D-aspartate
receptors to lower hepatic glucose production and triglyceride-rich lipoprotein
secretion in rats. Given that leptin and GLP-1 signalling in the DVC lowers
appetite, we tested whether DVC glycine sensing regulates food intake.
Male SD rats were implanted with stereotaxic cannulae into the DVC. After
a 22-h fast, glycine (10 Ојmol/L; n=6) or saline (n=5) was injected into the DVC,
and food intake was measured every hour for 6 h and at 20 h post-refeeding.
DVC glycine administration (10 Ојmol/L) increased DVC tissue glycine levels
1.5-fold (P<0.02). This was recapitulated by peripheral glycine administration
(50 nmol/kg, iv), which elevated circulating glycine levels 2-fold (741В±67 vs.
1291В±277 Ојmol/L, P<0.04) and similarly increased DVC glycine levels 1.5-fold
(P<0.02). Acute DVC glycine lowered cumulative food intake compared with
saline controls at 5 h (-30%; 17.3В±2.2 vs. 24.7В±1.6, P<0.03), 6 h (-35%; 19.7В±3.5
vs. 30.2В±2.3, P<0.05), and 20 h (-12%; 38.7В±1.6 vs. 44.2В±1.8 g, P<0.04) postrefeeding.
To evaluate the therapeutic potential of glycine delivery to lower food intake
in diet-induced obesity, we tested the effects of 1% (w/v) glycine in drinking
water in high fat diet-fed rats. This elevated plasma glycine levels 2.5-fold
(766В±29 vs. 1906В±153 Ојmol/L, P<0.005), comparable to the increase in DVC
tissue glycine levels achieved by direct DVC glycine administration. Dietary
glycine supplement for 24 h lowered food intake by 25% compared with
regular drinking water (17.0В±1.9 vs. 22.6В±0.9 g, P<0.04, n=5/group). Chronic
glycine intake for 8 d lowered cumulative 4-d food intake by 5% (P<0.05).
We provide novel evidence that glycine triggers a sensing mechanism in the
DVC to reduce appetite. Importantly, dietary glycine suppresses appetite in
diet-induced obesity. These findings suggest that glycine or a glycine analogue
may have nutraceutical benefits to lower food intake in obesity by triggering
the CNS.
Supported by: U.S. Dept. of Veterans Affairs; NIH
150-LB
Hepatic Fat Is a Determinant of Heaptic Insulin Sensitivity in PreВ­
Diabetes
ISABEL ERRAZURIZ CRUZAT, CHIARA DALLA MAN, SIMMI DUBE, CLAUDIO
COBELLI, ANANDA BASU, JOHN PORT, RITA BASU, Rochester, MN, Padua, Italy,
Padova, Italy
Hepatic fat has been implicated as a marker of insulin resistance. However,
the relationship between hepatic fat and hepatic insulin sensitivity (ability
of insulin to suppress hepatic glucose production) has not been assessed in
prediabetes. To do so, we studied individuals with prediabetes (n=15, 7M/8F,
age 58В±14 yrs, FPG 6.1В±0.5 mM , 2-hour glucose 9.3В±1.9mM, BMI 31В±3 kg/
m2, LBM 48В±8 kg) with a 3 hour labeled [6,6-2H2 glucose] 75 g oral glucose
tolerance test. [6,6-2H2 glucose] enrichment was measured by GCMS.
Endogenous glucose concentration was calculated by established methods.
Total hepatic fatty acid content was measured using single-breath-hold liver
magnetic resonance spectroscopy, with spectra processed using LCModel. The
methyl peak (Lip09) was used to quantify total fatty acid (FA) concentration.
Hepatic insulin sensitivity (SI Liver) was determined by both model independent
(iAUC endogenous glucose/iAUC insulin) method and our validated oral
model(1). Total hepatic FA was negatively correlated to SI Liver, the latter
measured with either model independent (r=0.64; p<0.02) method or with the
model (r=0.6; p<0.03). These data demonstrate that hepatic fatty acid content
is a determinant of hepatic insulin sensitivity in individuals with prediabetes.
Future studies are needed to determine whether interventions that lower
hepatic fatty acid content alter hepatic insulin action.
1. Dalla Man C, Toffolo G, Basu R, Rizza RA, Cobelli C: Use of labeled oral
minimal model to measure hepatic insulin sensitivity. Am J Physiol Endocrinol
Metab 2008;295:E1152-1159
Supported by: CIHR
153-LB
Microglia Modulate a Hypothalamic Inflammatory Response to
Saturated Fatty Acids in Mice
MARTIN VALDEARCOS, DANIEL K. NOMURA, ALLISON W. XU, SUNEIL K.
KOLIWAD, San Francisco, CA
High-fat diets promote the accumulation and inflammatory (M1) activation
of macrophages in peripheral tissues and of microglia, CNS analogs of
macrophages, in the hypothalamus. Saturated fatty acids (SFAs) trigger
macrophage activation, but what triggers microglial activation is unknown. We
found that feeding mice a 6-week diet rich in SFAs altered levels of several
lipid classes, including the SFA palmitic acid, specifically in the hypothalamus
in association with microglial activation and accumulation. Moreover, treating
primary murine microglia or hypothalamic slice cultures with long-chain SFAs,
but not unsaturated or short-chain species, increased M1 gene mRNA levels
and stimulated inflammatory cytokine secretion. We ablated hypothalamic
cultures of microglia by treatment with clodronate liposomes or by using
diphtheria toxin (DT) to treat slices from mice expressing diphtheria toxin
receptor under control of the CD11b promoter (CD11b-DTR). Microglial ablation
greatly reduced SFA-induced cytokine secretion, pointing to the importance
of hypothalamic microglia for the inflammatory response to SFAs. Microglial
ablation in slices was transient, and new microglia restored tissue content
within 10 days. We also lethally irradiated head-shielded CD11b-DTR mice,
and transplanted them with marrow lacking DTR. After recovery, microglia
were ablated by peripheral DT injection. As for slices, post-ablative microglial
proliferation occurred in vivo. Using donor marrow expressing RFP-coupled
MCP-1 receptors (CCR2-RFP), we confirmed that post-ablative microglial
proliferation does not involve peripheral monocytes. This proliferation
increased basal hypothalamic microglial content vs. DT-treated controls.
Our results indicate that SFAs stimulate microglia-dependent hypothalamic
Supported by: DK29953
Integrated Physiology—Macronutrient
Metabolism and Food Intake
151-LB
Hypothalamic Circadian Control of the Homeostatic Refeeding ReВ­
sponse and Insulin Resistance in Mice
WENYU HUANG, KATHRYN MOYNIHAN RAMSEY, LEI CHENG, BILIANA
MARCHEVA, CHIAKI OMURA, YUMIKO KOBAYASHI, RAVINDRA DHIR, REXFORD
S. AHIMA, JOSEPH T. BASS, Chicago, IL, Philadelphia, PA
The pacemaker clock within the central nervous system programs 24 hr
cycles of behavior and peripheral tissue metabolism across the sleep-wake/
fasting-feeding period. However, it is not clear how circadian signals regulate
mechanisms of energy and glucose homeostasis. Here we demonstrate that
the homeostatic refeeding response to fasting is regulated by circadian timing,
as acute 12 hr food consumption following a 24 hr fast is greater when feeding
resumes in the night time compared to the day time, despite equivalent leptin
For author disclosure information, see page LB66.
ADA-Funded Research
LB40
Integrated Physiology/Obesity
156-LB
inflammation and reveal a novel way to modulate microglial content as a tool
to test their role in diet-induced hypothalamic inflammation, neuronal injury,
and leptin resistance.
Differential Effects of Sleeve Gastrectomy and Duodenojejunal Bypass
on Fat Preference
Supported by: University of California, San Francisco
FEI WANG, MIN XU, JODY CALDWELL, STEPHEN C. WOODS, MYRTHA ARNOLD,
PATRICK TSO, Cincinnati, OH, Zurich, Switzerland
154-LB
Sleeve gastrectomy (SGx) and Duodenojejunal bypass (DJB) are commonly
performed bariatric procedures. In SGx, over 80% of the stomach is removed
without surgical reconfiguration of the intestine, whereas in DJB the stomach
is intact but ingested food bypasses the duodenum and upper jejunum. An
important question is whether altered size of the stomach or rearrangement
of the small intestine is more important in treating obesity and associated
disorders. Thus, comparing these two operations in one experiment provides a
unique opportunity to determine the relative importance of different segment
of the gastrointestinal tract (GI) in the regulation of body weight, food intake
and metabolism. We therefore performed SGx, DJB and sham procedures in SD
rats fed a chow diet in order to minimize any changes of body weight. Neither
SGx nor DJB induced significant weight loss or changes of resting or fasting
energy expenditure relative to sham surgery over 20 weeks in these chow-fed
rats. Additionally, SGx and DJB rats had similar daily food intake, and it was
comparable to that of sham-operated controls. However, compared with shamoperated rats, SGx rats had a significantly reduced preference for Intralipid
concentrations of over 10% as assessed using 2-bottle preference tests (P <
0.001). In contrast, DJB rats had comparable lipid preference as sham-operated
controls. SGx but not DJB also significantly reduced consumption of a high-fat
solid food (P <0.05) and consequently had increased intake of standard low-fat
chow consumption compared with sham controls (P<0.05). Thus, the present
results demonstrate that loss of the stomach may underlie reduced dietary
fat preference. The role of fat preference in mediating long-term maintained
weight loss after SGx requires further investigation. Understanding the different
physiologic mechanisms of these surgical procedures may help development
of less invasive treatments against obesity and associated complications.
Hypothalamic Mitochondrial Superoxide Accumulation Accompanies
Inflammation After Short Term Exposure to High-Fat Diet in Rats or
Palmitate in Clonal Hypothalamic Neurons
HEIDI KOCALIS, KEVIN NISWENDER, La Jolla, CA, Nashville, TN
Dietary saturated fat intake leads to low-grade hypothalamic inflammation
and is associated with CNS hormone resistance and impaired energy balance
regulation in rodents. Mitochondrial oxidative stress promotes inflammation
and insulin resistance in numerous peripheral tissues of obese mice, by
activating a family of redox sensitive inflammatory kinases including the c-Jun
N-terminal kinase (JNK) pathway. The role of oxidative stress in high-fat (HF)
induced hypothalamic inflammation has not been reported. We hypothesized
that oxidative stress is an early feature of diet-induced obesity (DIO) that
occurs within the first days after exposure to excess dietary fat. Long Evans
rats were fed a lard based high-saturated fat (HF: 45% kcal fat) or low-fat (LF:
10% kcal) control diet for 1 week. HF diet consumption increased hypothalamic
phosphorylation of JNK by 1.38В±0.14-fold and elevated mRNA expression of
the pro-inflammatory cytokine gene IL-6 by 4.0В±0.8-fold. We determined
hypothalamic superoxide (O2-) levels using the mitochondrial O2- specific
probe MitoSOX and HPLC. Hypothalamic O2- levels increased by 2.2-fold in
rats fed HF diet (LF: 6,158В±1,380 vs. HF: 13,754В±1,745; p<0.001). We extended
these findings in an in vitro setting, using the clonal mouse hypothalamic
cell line mHYPO E-42 treated with the saturated fatty acid palmitate (P) or
vehicle (BSA 100uM) for 12 hours. Palmitate treatment (100uM) increased
O2- by 1.45В±0.07-fold and increased JNK phosphorylation by 1.29В±0.09fold. Reducing O2- production with oleate or MitoTEMPO (25nM) prevented
palmitate induced inflammation and insulin resistance in vitro. Collectively,
this data provides evidence that mitochondrial O2- accumulation is a feature
of early DIO that may contribute to hypothalamic inflammation. More work
is needed to ascertain the role of ROS in hypothalamic hormone resistance
associated with the development of DIO.
157-LB
Chronic Advanced Glycation Endproducts (AGE) Exposure Promotes
Spinal Degeneration in Insulin-Resistant Non-Hyperglycemic Mice
YOUNG LU, SVENJA ILLIEN-JUNGER, SHEERAZ A. QURESHI, WEIJING CAI,
HELEN VLASSARA, GARY E. STRIKER, JAMES C. IATRIDIS, New York, NY
Supported by: NIH (DK085712), (DK069927), (DK007563)
Intervertebral disc (IVD) degeneration is a major cause of back pain. Modern
diets contain high levels of advanced glycation end products (AGEs), contributors
to diabetes and aging complications. We previously showed diabetes related
IVD degeneration in mice is associated with AGE accumulation. This study
investigates the role of AGEs on IVD independent of hyperglycemia.
C57BL6 mice were fed isocaloric diets with standard amount of AGEs
methylglyoxal (MG+ 1.8x104 nmol/day) or reduced AGEs (MG- 0.65x104
nmol/day p<.01) for 5 generations. F5 mice were sacrificed at 18 months.
MG+, but not MG- mice, were insulin resistant but not hyperglycemic, and
had higher serum MG (1.59В±0.2 vs. 0.83В±0.2 nmol/ml), and weight (35.1В±1.8
vs. 29В±0.52g) p<.05. Lumbar spines were analyzed using ВµCT, histology, and
immunohistochemistry (MG).
MG+ spines had reduced proteoglycan content of the nucleus pulposus (Fig.
1) and higher vertebral cortical thickness and area than MG- (p<.05). AGE/MG+
mice exhibited greater MG accumulation in vertebral endplates, higher bone
mineral density (p<.01) and lower connectivity density in superior endplates
(p<.01) than MG- mice.
Chronic exposure to oral AGEs promotes early IVD degeneration in parallel
with insulin resistance, independent of hyperglycemia. Reduced oral AGEs
were IVD protective. More studies are needed to mechanistically establish the
role of AGEs in IVD relative to metabolic syndrome and diabetes.
155-LB
Cardiometabolic Dysfunction After Just 2 Weeks of High Fat Feeding
JOSIANE L. BROUSSARD, MICHAEL D. NELSON, CATHRYN KOLKA, ISAAC
B. ASARE, EDWARD W. SZCZEPANIAK, LIDIA S. SZCZEPANIAK, RICHARD N.
BERGMAN, Los Angeles, CA
Cardiovascular disease is a major complication of Type 2 Diabetes
Mellitus (T2DM). Increased dietary fat consumption is a risk factor for each
of these diseases and we propose that it is a common mechanism during the
development of both. Thus, it is critical to identify areas of intervention during
the early stages of cardiometabolic disease progression. We hypothesize
that high fat feeding will lead to an immediate and observable decrease in
cardiometabolic function in as little as 2 weeks.
Intravenous glucose tolerance tests and cardiac magnetic resonance imaging
(cMRI) were conducted in eight male dogs at baseline (W0), and after 2, 6
and 24 weeks of fat feeding (W2, W6, W24). Normal chow consisted of 40%
carbohydrate, 32% fat and 28% protein. For fat feeding, 6g/kg of rendered pork
fat was added to control chow for a final composition of 52% fat. Food was
presented each day from 9a-10a. Dogs were presented with 3,578 calories/day
during control and 5,025 calories/day during fat feeding.
High fat feeding resulted in significant weight gain (5% at W2, 8% at W6,
13% at W24; p<0.001) in both visceral and subcutaneous depots (by MRI), as
well as decreases in insulin sensitivity (-18%, -21% and -41% at W2, W6 and
W24, respectively and reaching significance by W6; p<0.05). Left ventricular
function (circumferential strain by tissue tagging) was also impaired with high
fat feeding, with the largest decrease in function occurring at 2 weeks (-18%
at W2, -26% at W6, -16% at W24 [n=4 for W24 cardiac data]; p<0.05). No
changes were observed in left ventricular mass, dimensions, blood pressure
or heart rate.
These results support our hypothesis that acute high fat feeding impairs
cardiometabolic function, and provides new insight into the development of
cardiovascular disease in T2DM.
Supported by: NIH/NIAMS (RO1AR051146), (RO1AG023188); JDRF (17-20081041)
Supported by: NIDK27619, NIDK29867; Society in Science (to J.L.B.)
For author disclosure information, see page LB66.
ADA-Funded Research
LB41
Integrated Physiology/Obesity
Integrated Physiology—Muscle
158-LB
Insulin Resistance Following Exposure to the Common Food Additive
Carrageenan Demonstrated by Hyperinsulinemic, Euglycemic Clamp
Studies
160-LB
Fasting-Induced Mitochondrial Dysfunction Is Reversed by AMPK
Activation in Mouse Skeletal Muscle
JOANNE K. TOBACMAN, SUMIT BHATTACHARYYA, LEONID FEFERMAN, LI
KANG, DAVID H. WASSERMAN, TERRY G. UNTERMAN, Chicago, IL, Nashville,
TN
HANS P. LAURITZEN, LAURIE J. GOODYEAR, Boston, MA
Mitochondrial dysfunction is proposed to be both a cause and consequence
of insulin resistance and recent data suggest that mitochondrial morphology
is critical in organelle function. We determined the effects of fasting-induced
insulin resistance and AMPK activity on mitochondrial morphology and function
using intravital microscopy. Subsarcolemma (SS) and intramyofibrillar (IMF)
mitochondria were imaged in muscle fibers using a mitochondrial-specific GFP
tag or by average NADH-positive organelle area (pixel area). Mitochondria
oxidation was measured by the level of NADH autofluorescence (AF; grey
value/Вµm2). Mice were studied in the fed state or after a 24 hr fast that
induced marked glucose intolerance (p<0.003). Fasting caused mitochondrial
fragmentation as indicated by a 62% (SS) and 43% (IMF) decrease in NADH
area (p<0.01). Fasting also caused a 70% (SS) and 84% (IMF) decrease in
mitochondrial oxidation (p<0.02). The AMPK activator AICAR (1gr/kg i.v.)
rapidly (30 min) normalized both the fasting-induced fragmentation and
decreased oxidation. To determine the effects of AMPK activity independent of
nutritional state, skeletal muscle-specific transgenic (TG) mice with increased
or decreased AMPK activity were studied in the fed state and compared to
their respective littermate controls. TG mice with increased AMPK activity
had mitochondrial elongation [SS:492%, IMF:324% increase in NADH area;
(p<0.003)] and increased oxidation [SS:237%, IMF:212% increase in NADH AF;
(p<0.03)]. TG with decreased AMPK activity had mitochondrial fragmentation
[SS:40%, IMF:65% decrease in NADH area p<0.003)] and decreased oxidation
[SS:51%, IMF:57%, decrease in NADH AF (p<0.03, p=0.34; respectively)].
Fasting did not further alter mitochondria morphology and oxidation in TG mice.
In conclusion, fasting-induced insulin resistance causes rapid mitochondrial
dysfunction that is reversed by AMPK activation. AMPK is an important
regulator of mitochondrial morphology.
The common food additive carrageenan produced glucose intolerance,
insulin resistance, and impaired insulin signaling in C57BL/6 mice treated with
high molecular weight carrageenan in the water supply (10 Ојg/ml) for 18 days.
To analyze further the impact of carrageenan, hyperinsulinemic, euglycemic
clamp studies were performed. Studies were performed in 24 mice (twelve
treated and twelve controls) that were fasted for 5 h. Mice had indwelling
jugular vein and carotid artery lines, and insulin was infused at 4mU/kg/min and
the glucose infusion rate was adjusted to achieve glucose homeostasis with
glucose measured at 10 minute intervals. The carrageenan-treated animals
demonstrated: significantly higher arterial glucose levels due to a reduced
glucose clearance and lower endogenous glucose production rates at baseline.
The time course of glucose infusion rate to achieve a steady state glucose
concentration during the clamp was slowed with carrageenan-treatment.
Other studies demonstrated that in mice given carrageenan in their water,
controls and treated animals had similar glucose tolerance at 3 days, but by six
days, carrageenan-treated animals had significantly higher glucose levels at
all time points. The chemokine IL-8 (or KC, the mouse homolog) was increased
following carrageenan exposure, and experiments in human hepatocytes
showed that IL-8 treatment inhibited production of phospho(Ser473)-AKT
and PI3K activity following insulin, suggesting that some of the effects that
follow carrageenan may be mediated by IL-8. Future studies will further
clarify the mechanisms by which oral carrageenan exposure induces systemic
inflammation with extracolonic effects, including impaired insulin signaling,
and may contribute to development or progression of clinical diabetes.
159-LB
The FGF21 Response to Fructose in Humans: Defining a Fructose
Tolerance Test
Supported by: NIH
JODY DUSHAY, ELENA TOSCHI, EMILIE K. MITTEN, FFOLLIOTT M. FISHER,
ELEFTHERIA MARATOS-FLIER, MARK A. HERMAN, Boston, MA
161-LB
eIF2О± Phosphorylation in Skeletal Muscle Increases FGF21 Expression
as a Myokine and Prevents Diet-Induced Obesity by Increasing Energy
Expenditure
Recent evidence implicates high fructose consumption as a risk factor for
obesity, diabetes and metabolic syndrome (MetS). Currently, there is no method
to quickly assess an individual’s biological response to fructose. Fibroblast
growth factor 21 (FGF21) is a metabolic hormone involved in lipid and glucose
metabolism. In humans, FGF21 levels positively correlate with features of
MetS, however its regulation is poorly understood. Dietary manipulations such
as fasting and ketogenic diet increase FGF21 in rodents but have little or no
effect in humans. In rodents, FGF21 levels increase markedly with fructose
consumption. We therefore hypothesized that fructose ingestion might regulate
FGF21 levels in humans. We administered a 75g oral fructose load to 10 lean
subjects. Serum FGF21 rose within 90 min and peaked at 120 min with a fourfold increase over baseline [P < 0.0002]. In contrast, a 75 gram oral glucose
load had no effect on FGF21 at this time point. We next evaluated the FGF21
response following oral fructose in 7 subjects with MetS. The FGF21 excursion
was higher in MetS compared to lean controls [FGF21 AUC: Control 53.4 В± 2.4
min*ng/ml vs. MetS 141.7 В± 11.5, P < 0.007]. We also compared the FGF21
excursion following ingestion of a combined fructose + glucose load (37.5g
of each). While there was an 8-fold variation in the FGF21 excursion across
subjects, for any given individual there was a strong correlation between the
response following fructose and the response following the mixture (R2=0.75,
P<0.001). The variability across but reproducibility within individuals indicates
that genetic or chronic environmental factors, such as long-term dietary
composition, may govern an individual’s FGF21 response to fructose. To our
knowledge, FGF21 is the only known measurable circulating biomarker that
specifically assesses an individual’s acute metabolic response to fructose
ingestion. This bioassay will form the foundation for a new paradigm for
investigating fructose-associated metabolic disease.
MASATO MIYAKE, AKITOSHI NOMURA, ATSUSHI OGURA, KAZUNA TAKAHARA,
KIYOE KURAHASHI, RYOSUKE SATO, MIHO OYADOMARI, HIROSHI INOUE,
SEIICHI OYADOMARI, Tokushima, Japan
EndoplasmicВ reticulum (ER) stress has emerged as an important cause
of diabetes. Unfolded protein response is an adaptive process in response
to ER stress that is activated by three transducers, IRE1, ATF6, and PERK.
We previously reported that the expression of gluconeogenic and lipogenic
genes in liver (Cell Metab (2008) 7 520-532) requires PERK-mediated eIF2О±
phosphorylation, but the role of PERK signaling pathway in skeletal muscle
remains unclear. In this study, we generated skeletal muscle-specific
transgenic (TG) mice that overexpress Fv2E-PERK, which promotes eIF2О±
phosphorylation by the artificial ligand AP20187 uncoupled from ER stress in a
dose-dependent manner. These TG mice are a powerful tool to dissect the role
of PERK signaling; we found that eIF2О± phosphorylated TG mice were resistant
to high-fat diet-induced obesity because of increased energy expenditure. In
skeletal muscle, the fiber type composition and metabolic gene expression of
TG mice were similar to those of wild-type mice. However, mRNA expression of
thermogenic genes in brown adipose tissue was higher in TG mice. Microarray
analysis of mRNA expression in the skeletal muscle of TG mice revealed
higher expression of the metabolic hormone Fgf21, which is known to have
antidiabetic, antihyperlipidemic, and antiobesity effects. Consistent with this,
plasma FGF21 concentration was markedly increased in TG mice. Promoter
analysis identified that eIF2О± regulates Fgf21 in a downstream transcription
factor, ATF4,-dependent manner. Our results show that eIF2О± phosphorylation
in skeletal muscle prevents obesity by increasing energy expenditure of brown
adipose tissue but not skeletal muscle. We conclude that this phenotype is
mediated via FGF21 from skeletal muscle, suggesting that FGF21 is an ER
stress/PERK/eIF2О±-induced myokine and that phosphorylation of eIF2О± is a
potential therapeutic target for diabetes and obesity.
Supported by: JPB Foundation
For author disclosure information, see page LB66.
ADA-Funded Research
LB42
Integrated Physiology/Obesity
162-LB
whether aging affects the gene expression of muscle FNDC5 and PGC1О± and;
2) examine whether exercise up regulates the expression of these genes in
aging. Insulin sensitivity (M) was measured with a hyperinsulinemic (40 mU/
mg.min) euglycemic clamp and vastus lateralis muscle biopsies were performed
in 24 young, non diabetic (age= 26В±3 y, BMI= 24.1В±0.5 kg/m2, VO2max=25.4В±2
ml/kg.min, M/I=16.87В±1.7 mg/kg FFM.min/mU/ml x100) and 48 older, non
diabetic (age=73В±7, BMI=24.4В±0.4, VO2max=17.1В±0.9, M/I=14.1В±2.3) subjects.
In 17 older and 10 younger, these measurements were done before and after
16 week aerobic exercise program. At baseline, both PGC1 and FNDC5 mRNA
level were significantly lower in older (50% and 24% of younger, respectively;
P<0.05). PGC1О± mRNA directly correlated with FNDC5 (r=0.61, P<0.0001). Both
PGC1 and FNDC5 mRNA negatively correlated with age (r=-0.51, P< 0.0001;
r=-0.27, P< 0.02, respectively). Exercise program increased PGC1О± and FNDC5
expression in a both older (40% and 30%, respectively; P<0.05) and younger
(50% in both; P<0.05), accompanied by an increase in M/I (20% in older and
22% in younger) and VO2 (11% in older and 18% in younger). Conclusions: 1)
Aging is associated with decreased PGC1 and FNDC5 gene expression, and
these molecular changes could be involved in the metabolic alterations that
occur during aging; 2) Exercise enhances the gene expression of PGC1 and
FNDC5, an effect that possibly contributes to the beneficial metabolic effects
of exercise in the elderly.
High-Fat Diet-Induced Impairment of Skeletal Muscle Insulin Action
Is Not Prevented by SIRT1 Overexpression
AMANDA T. WHITE, SIMON SCHENK, La Jolla, CA
SIRT1 has been implicated in the regulation of skeletal muscle metabolism
in response to changes in nutrient availability, though its role in the modulation
of skeletal muscle insulin action remains to be completely defined. Previous
studies have demonstrated that SIRT1 expression decreases under insulinresistant conditions, such as those induced by a high-fat/hypercaloric diet
(HFD). Thus, we sought to determine whether augmenting skeletal muscle
SIRT1 levels via constitutive activation in a mouse model would prevent HFDinduced skeletal muscle insulin resistance. To address this, mice with musclespecific overexpression of SIRT1 (mOX) and their wildtype (WT) littermates
were fed low-fat control diet (CON; 10% calories from fat) or a HFD (60%
of calories from fat) for 12 weeks beginning at 10 weeks of age. Magnetic
resonance imaging and indirect calorimetry were used to measure body
composition and energy expenditure (EE), respectively. Insulin-stimulated
glucose uptake was measured using a 2-deoxyglucose uptake assay at a
physiological insulin concentration of 0.36 nmol/L (60 ОјU/mL) in isolated
soleus and extensor digitorum longus (EDL) muscles. SIRT1 protein abundance
was ~50-300-fold higher in soleus and EDL muscles from mOX vs. WT mice. As
expected, body weight and percent body fat were increased by 30% and 300%,
respectively, in HFD v. CON animals, while there was no effect of genotype on
these parameters. In addition, EE was not affected by diet or genotype, though
HFD increased the contribution of fat to total EE. Importantly, 12 weeks of HFD
decreased insulin-stimulated glucose uptake in skeletal muscle by 50%, and
this impairment was not prevented in mOX mice. These impairments in insulin
action were paralleled by decreased insulin-mediated activation of Akt and
GSK3ОІ. Taken together, the present results demonstrate that upregulation of
SIRT1 activity in skeletal muscle does not prevent HFD-induced impairments in
skeletal muscle insulin action.
Supported by: NIA; NIDDK
HO-JIN N. KOH, MIN-YOUNG LEE, MICHAEL F. HIRSHMAN, LAURIE J. GOODYEAR,
Boston, MA
TRB3 is known to regulate metabolism in multiple tissues and we have
recently shown that TRB3 is important for Endoplasmic Reticulum (ER) stressorinduced insulin resistance in skeletal muscle. However, the role of TRB3 in
nutritional stress-induced insulin resistance remains unclear. To determine
the role of TRB3 in high fat diet-induced obesity and insulin resistance, we
studied global TRB3 knockout (TRB3KO) mice fed a high fat diet (HFD; 60%
fat by kcal) for eight weeks. TRB3 mRNA expression in skeletal muscle was
significantly increased by HFD in wild type mice by 5.2-fold (P<0.05). TRB3KO
mice exhibited lower body weight (11%) and fasting blood glucose (205 В± 9
vs. 151 В± 14 mg/dl), and improved glucose tolerance (35% decrease in AUC)
compared to wild type, with no difference in food intake. Serum leptin, insulin,
and total cholesterol were lower and adiponectin concentrations higher in
TRB3KO mice, indicating improved whole body glucose and lipid metabolism.
Skeletal muscle from TRB3KO mice had normal levels of GLUT1, GLUT4,
glycogen, triglycerides, and mRNA expression of ER stress markers. However,
muscles from TRB3KO mice had increased insulin-stimulated glucose uptake
and phosphorylation of IRS1 (Y612), Akt (T308), FoxO1 (S256), and FoxO3a
(S253), demonstrating improved insulin sensitivity. Liver triglycerides were
decreased by 57% and tissue weight 49% lower, suggesting TRB3KO mice
are protected from HFD-induced steatosis. There were no differences in mRNA
expression of genes involved in ER stress and gluconeogenesis, but decreased
expression of lipogenic genes (SREBP1, FAS, ACC, and SCD1) in livers from
TRB3KO mice. In conclusion, TRB3KO mice are protected from high fat dietinduced muscle insulin resistance and hepatic steatosis. TRB3 is a potential
target for type 2 diabetes treatment.
Supported by: R01AG043120
163-LB
BAF60c Drives Glycolytic Muscle Formation and Improves Glucose
Homeostasis through Deptor-Mediated AKT Activation
ZHUOXIAN MENG, SIMING LI, LIN WANG, HWI JIN KO, YONGJIN LEE, DAE
YOUNG JUNG, MITSUHARU OKUTSU, ZHEN YAN, JASON K. KIM, JIANDIE LIN,
Ann Arbor, MI, Worcester, MA, Charlottesville, VA
A shift from oxidative to glycolytic metabolism has been associated with
skeletal muscle insulin resistance in type 2 diabetes. However, whether this
metabolic switch is deleterious or adaptive remains controversial, in part due to
limited understanding of the regulatory network that directs the metabolic and
contractile specification of fast-twitch glycolytic muscle. Here we show that
BAF60c, a transcriptional cofactor enriched in fast-twitch muscle, promotes
a switch from oxidative to glycolytic myofiber type through Deptor-mediated
AKT activation. Muscle-specific transgenic expression of BAF60c activates
a program of molecular, metabolic, and contractile changes characteristic of
glycolytic muscle. In addition, BAF60c is required for maintaining glycolytic
capacity in adult skeletal muscle in vivo. BAF60c expression is significantly
decreased in skeletal muscle from obese mice. Unexpectedly, transgenic
activation of the glycolytic muscle program by BAF60c protects mice from
diet-induced insulin resistance and glucose intolerance. Further mechanistic
studies revealed that Deptor is induced by the BAF60c/Six4 transcriptional
complex and mediates activation of AKT and glycolytic metabolism by BAF60c
in a cell-autonomous manner. This work defines a fundamental mechanism
underlying the specification of fast glycolytic muscle and illustrates that the
oxidative to glycolytic metabolic shift in skeletal muscle is potentially adaptive
and beneficial in the diabetic state.
Integrated Physiology—Other Hormones
166-LB
Testosterone Restores Insulin Sensitivity in Males With HypoВ­gonadoВ­
tropic Hypogonadism (HH) Through Its Novel Anti-Inflammatory
Actions and the Suppression of Free Fatty Acids (FFA), Tumor Necrosis
Factor (TNF) О±, Suppressor of Cytokine Signaling (SOCS)-3 and IОєB
Kinase (IKK) ОІ Independently of Weight Loss
Supported by: NIH; AHA
165-LB
Deletion of Tribbles 3 (TRB3) Protects Mice from High Fat Diet-Induced
Insulin Resistance and Hepatosteatosis
164-LB
Effect of Age and Exercise on FNDC5 and PGC1alpha Gene Expression
in Human Skeletal Muscle
SANDEEP DHINDSA, HUSAM GHANIM, KELLY GREEN, SANAA ABUAYSHEH,
NITESH KUHADIYA, SARTAJ SANDHU, MANAV BATRA, ANTOINE MAKDISSI,
AJAY CHAUDHURI, PARESH DANDONA, Buffalo, NY
SANGEETA GHOSH, HELEN LUM, HANYU LIANG, JOSE DE JESUS GARDUNO
GARCIA, RAWEEWAN LERTWATTANARAK, YOLANDA CIPRIANI, NICOLAS
MUSI, San Antonio, TX
We have recently demonstrated that HH occurs in one third of men with
type 2 diabetes (T2D) and these patients have a significantly greater intensity
(by 30%) of insulin resistance. We have now asked the question whether the
replacement of testosterone (T) in such patients reverses insulin resistance
and whether the factors known to be inflammatory and to interfere with
insulin signal transduction are suppressed by T. 20 men with T2D and HH
were randomized to receive intramuscular T (250 mg) or placebo (1ml saline)
every 2 weeks for 6 months (n=10 in each group). Insulin sensitivity was
calculated from the glucose infusion rate(GIR) during the last 30 min of a 4 hour
For author disclosure information, see page LB66.
Older subjects are at increased risk of developing insulin resistance and
type 2 diabetes. Peroxisome proliferator-activated receptor Оі coactivator 1
О± (PGC1О±) is a master regulator of energy metabolism and some evidence
indicates that PGC1О± is down regulated with aging. In mouse muscle,
overexpression of PGC1О± enhances the mRNA level of fibronectin type III
domain containing 5 (FNDC5), a gene that encodes for irisin, a protein that
is secreted into the circulation. The goals of this study were to: 1) examine
ADA-Funded Research
LB43
Integrated Physiology/Obesity
hyperinsulinemic-euglycemic clamp(80mU/m2/min) and expressed as mg/kg
body weight/min. GIR increased by 30% after 6 months (4.1В±2.0 vs. 5.3В±2.3
mg/kg/min, p=0.005) of T therapy but did not change in placebo group(3.4В±1.5
vs. 3.5В±1.8 mg/kg/min, p=0.88). FFA, CRP and TNF-О± concentrations decreased
(0.63В±0.10 vs. 0.41В±0.04 mM/L, 3.78В±1.34 vs. 2.90В±1.08 mg/L and 2.56В±0.39
vs. 2.18В±0.31 pg/mL respectively, p<0.05 for all) after T therapy. There was
a decrease in mRNA expression in mononuclear cells of SOCS-3 (-27%) and
IKKОІ (-23%), two proteins known to interfere with insulin signaling and to
cause insulin resistance. PPARО± increased by 38% but there was no change
in c-Jun N-terminal kinase (JNK)-1 and PPARОі expression after T therapy.
There was no significant change in any of the inflammatory mediators in the
placebo group. There was no change in weight in either group. Thus, our data
define for the first time that T restores insulin sensitivity in T2D men with HH
independently of weight loss and due to the suppression of FFA, TNFО± and CRP
concentrations and the expression of SOCS-3 and IKKОІ.
which reduced after GBP only, including Fetuin A and Retinol binding protein
4 (RBP4), both known to be associated with insulin resistance. Reductions in
Fetuin A (25.7В±3.8%, p=0.02) and RBP4 (50.5В±6.9%, p=0.02) after GBP were
confirmed using ELISA and immunoassay respectively. Metabolomic analysis
identified significant reduction of citrate, proline, histidine and decanoic
acid specifically after GBP. Greater reduction of fetuin A, RBP-4, and several
metabolites occur early after GBP compared to SG, independent of weight loss,
and may contribute to enhanced T2D remission observed following foregut
bypass (GBP) procedures.
Supported by: Novo Nordisk, Inc.
169-LB
One Week of Effective Treatment of Obstructive Sleep Apnea in
Patients With Type 2 Diabetes Results in Enhanced Post-Prandial GIP
Release
Supported by: NIH
FANNY DELEBECQUE, VARGHESE ABRAHAM, SUMA DRONAVALLI, CAROL
TOUMA, BABAK MOKHLESI, ESRA TASALI, EVE VAN CAUTER, Chicago, IL
167-LB
Post-prandial release of Glucose-dependent Insulinotropic Polypeptide (GIP)
is reduced in type 2 diabetes mellitus (T2DM). Approximately two-thirds of
patients with T2DM have obstructive sleep apnea (OSA). An adverse impact of
OSA on glycemic control has been documented but the underlying mechanisms
are unclear. Continuous positive airway pressure (CPAP) treatment of OSA may
improve glucose metabolism but efficacy has been limited by insufficient use.
We investigated the impact of effective CPAP treatment on post-prandial GIP
levels in patients with OSA and T2DM to determine whether reduced incretin
release is involved in the adverse impact of OSA on glycemic control.
Individuals with T2DM (n=15; Age: 54.3В±2.3 years, BMI: 38.7В±2.5 kg/m2,
HbA1c: 7.6В±0.4 %, apnea hypopnea index: 44.7В±6.1/hour) were randomized
in a 2:1 ratio to 1-week of active CPAP (n=11) or sham-CPAP treatment (n=4).
Both groups spent each night in the laboratory with optimum CPAP adherence.
Body weight and medications did not change over the study period. Prior to
randomization and after one week of treatment, the participants underwent
a 24h period of blood sampling at 15-30 min intervals while identical highcarbohydrate meals were ingested at 0900h, 1400h, and 1900h. Each sample
was immediately centrifuged at 4В°C and kept frozen at -20В°C until assay.
Measurements of plasma GIP levels were performed using a multiplex
technology (Millipore, Billerica, MA).
Mean 24-h GIP levels were significantly higher (p=0.005) after one week
of rigorously controlled active CPAP treatment due to an elevation of postprandial levels (p=0.01; + 17.1В±5.4 %) without change in overnight fasting
levels (p=0.5). No consistent changes in post-prandial GIP levels were observed
following sham CPAP treatment.
The findings suggest that impaired GIP release is involved in the adverse
impact of OSA on glycemic control in T2DM.
Potent, Insulin-Independent Glucose-Lowering Mediated by FGF19
Action in the Brain
GREGORY J. MORTON, MILES E. MATSEN, DEANNA P. BRACY, THOMAS H.
MEEK, DARKO STEFANOVSKI, RICHARD N. BERGMAN, DAVID H. WASSERMAN,
MICHAEL W. SCHWARTZ, Seattle, WA, Nashville, TN, Los Angeles, CA
The gut-derived hormone fibroblast growth factor-19 (FGF19) has potent
anti-diabetic effects in leptin-deficient ob/ob mice that are hypothesized to
involve the FGFR1 receptor isoform. Since FGFR1 is concentrated in mediobasal
hypothalamic areas involved in glucose homeostasis, we sought to determine
whether the glucoregulatory effects of systemic FGF19 administration involves
an action in the brain, and if so, to clarify the underlying mechanism(s). We
performed a series of studies in ob/ob mice following implantation of a
cannula in the lateral ventricle. As expected, systemic FGF19 administration
(1 mg/kg) lowered blood glucose levels and improved glucose tolerance
relative to vehicle-treated controls (P<0.05). This effect was attenuated by
an intracerebroventricular (icv) pre-treatment injection of an FGFR inhibitor
(PD1731074; 25Ојg) at a dose that had no effect when given alone, suggesting
that the systemic effect involves a central mechanism. Consistent with this
hypothesis, icv administration of a much lower dose of FGF19 (3Ојg) lowered
blood glucose and improved glucose tolerance in ob/ob mice (p<0.05), while
the same dose had no effect when administered peripherally. To clarify the
mechanism of glucose lowering, we performed a frequently sampled IVGTT 2-h
after icv injection of either FGF19 or vehicle, and analyzed glucose and insulin
data using the Minimal Model. Central infusion of FGF19 induced a marked
increase of glucose tolerance despite no change of either insulin secretion or
insulin sensitivity. Rather, the glucose lowering effect resulted entirely from
a 3-fold increase of glucose effectiveness (p<0.05), the insulin-independent
component of glucose tolerance. We conclude that 1) the anti-diabetic effect
of FGF19 involves a central site of action, 2) the brain has the capacity to
rapidly and potently induce glucose lowering through an entirely insulinindependent mechanism, and 3) the beneficial effect of central FGF19 action is
mediated via this mechanism.
Supported by: ULl-RR024999; PO1AG-11412; P60-DK020595; Philips Respironics
170-LB
Exendin-4 (Ex4) Improves Cardiac Function in a Mouse Model of
Inflammatory Cardiomyopathy
CRAIG W. YOUNCE, JIANLI NIU, PAPPACHAN E. KOLATTUKUDY, JULIO E. AYALA,
Orlando, FL
Supported by: NIH (DK083042), (DK089053)
Type 2 diabetes is associated with chronic inflammation that affects organs
such as the heart. Monocyte chemotactic protein-1 (MCP1) is a pro-inflammatory
factor that contributes to the development of diabetic cardiomyopathy by
facilitating hyperglycemia-induced cardiomyocyte endoplasmic reticulum
(ER) stress and apoptosis. Activation of the glucagon-like peptide-1 receptor
(GLP1R) by Ex4 prevents hyperglycemia-induced cardiomyocyte ER stress
and apoptosis. The present study tests the hypothesis that Ex4 is also
cardioprotective in a mouse model of inflammatory cardiomyopathy. Cardiac
specific overexpression of MCP1 (MHC-MCP1) increases monocyte infiltration,
ER stress, cardiac fibrosis and left ventricular dysfunction. Three month-old
MHC-MCP1 mice were implanted with osmotic minipumps delivering either
Ex4 (24 nmol/(kgВ·day)) or PBS for 12 weeks and were compared to wild-type
mice receiving PBS (WT). Compared to WT, MHC-MCP1 mice receiving PBS
exhibited decreased fractional shortening (FS: 48.5В±1.2 vs. 32.3В±1.0%; p<0.05)
and ejection fraction (EF: 84.3В±1.2 vs. 67.3В±1.2%; p<0.05). MHC-MCP1 mice
receiving Ex4 displayed FS and EF values comparable to WT (42.6В±1.2%
and 82.6В±1.3%; p<0.05 vs. MHC-MCP1 PBS). Despite the improved cardiac
function, MHC-MCP1 mice infused with Ex4 did not exhibit a decrease in
monocyte infiltration or cardiac fibrosis. However, compared to MHC-MCP1
mice receiving PBS, MHC-MCP1 mice receiving Ex4 displayed reduced
apoptosis as indicated by lower TUNEL staining (3.3В±0.3 vs. 0.6В±0.1%; p<0.05)
and caspase 3 cleavage (2.9В±0.6 vs. 0.6В±0.5 cleaved:uncleaved; p<0.05). Ex4
also attenuated expression of the ER stress markers GRP78, PDI and CHOP. In
sum, Ex4 improves cardiac function and reduces ER stress and cardiomyocyte
168-LB
Acute Reduction in Fetuin A, Retinol Binding Protein 4 and Several
Metabolites After Gastric Bypass But Not Sleeve Gastrectomy in
Obese Patients With Type 2 Diabetes
SHELLEY YIP, MIA JULLIG, GREG SMITH, MARTIN MIDDLEDITCH, RINKI MURPHY,
Auckland, New Zealand
Bypass of foregut secreted factors promoting insulin resistance is
hypothesized to be one of the mechanisms by which diabetes resolution
follows roux-en-y gastric bypass (GBP) surgery. We wished to identify proteins
or metabolites linked with insulin resistance which reduced after laparoscopic
GBP,compared to sleeve gastrectomy (SG) with intact foregut, using quantitative
proteomic and metabolomic analyses. Plasma from 15 subjects with type 2
diabetes (T2D), matched for BMI, oral diabetes therapy and glycemic control,
undergoing GBP or SG was analyzed 3 days before and after surgery. Insulin
sensitivity was estimated using homeostatic model assessment (HOMA-IR).
Samples were depleted of abundant plasma proteins, trypsin digested and
labeled with iTRAQв„ў isobaric tags prior to liquid chromatography-coupled mass
spectrometry analysis. Gas chromatography and mass spectrometry were used
for metabolomic analysis. Relative change after surgery was calculated for both
proteomic and metabolomic data and compared between GBP and SG. Postoperative diabetes therapy was discontinued in all. Although mean reduction
in HOMA-IR was greater following GBP than SG, this did not reach statistical
significance (3.44 vs. 0.47, p=0.39). Proteomic analysis yielded 7 proteins
For author disclosure information, see page LB66.
ADA-Funded Research
LB44
Integrated Physiology/Obesity
173-LB
apoptosis in MHC-MCP1 mice. This demonstrates a novel anti-inflammatory
role for Ex4 and proposes that the GLP1R is a viable target for the treatment
of cardiomyopathies associated with inflammatory diseases such as type 2
diabetes.
Comparable Gastrointestinally Mediated Glucose Disposal in
South Asians and Caucasians—Preliminary Findings From a Study
Investigating Racial Differences in the Incretin System in South
Asians
171-LB
RUPA AHLUWALIA, FILIP K. KNOP, TINA VILSB�LL, L. RANGANATH, JURIS J.
MEIER, JITEN VORA, Liverpool, United Kingdom, Hellerup, Denmark, Bochum,
Denmark
Synergistic Glucose-Lowering Effects of SGLT1- and ASBT-Inhibitor
Combinations in ZDF Rats
South Asians are at an increased risk of type 2 diabetes that develops early
and at lower levels of obesity with an increased risk of complications. There
is emerging evidence from clinical and genomic studies, to suggest a possible
�racial’ variation in the incretin system. However most of the data comes from
Japan & Korea with limited evidence of incretin studies in South Asians who
differ metabolically from Far East Asians.
We hypothesised that the incretin system varies in South Asians, which
may be due to a difference in the incretin effect, endogenous postprandial
responses of individual incretin hormones, and/or insulinotropic or alpha cell
responses to circulating incretin hormones. Preliminary data from our study
comparing the incretin effect in both groups is presented below.
Nine South Asian subjects (age: 34+/-4 years (Mean+/- SEM); BMI 25+/1.2 kg/m2; waist-hip ratio (WHR) 0.87+/- 0.02) and eight age & BMI matched
Caucasian subjects (age: 29+/-4 years; BMI 23+/-0.96 kg/m2; WHR 0.90+/0.02) were studied. All were confirmed to have normal oral glucose tolerance
following a 75 gm. glucose load.
All subjects underwent a 4- hr. paired oral glucose tolerance test (50 gm.)
and isoglycaemic i.v. glucose (20%) infusion study involving sampling for
insulin, c-peptide, glucagon, GLP-1 & GIP, on 2 separate days. Blood glucose
was measured using an YSI STAT analyser.
Gastrointestinally mediated glucose disposal was calculated using the
formula 100x(glucoseOGTT- glucoseIGII)/glucoseOGTT with glucoseOGTT being 50
gm. for all subjects.
There were no significant differences in the gastrointestinally mediated
glucose disposal (GIGD%)(South Asians 60.3+/- 4.9; Caucasians 56.8+/-5.3).
GIGD is one of the ways of describing the incretin effect. Given our findings,
other aspects of incretins need to be studied to confirm potential �racial’
differences in incretin biology.
LIHONG CHEN, YAPING J. LIU, JUDI MCNULTY, DAVID COWAN, JON COLLINS,
ROBERT L. DOBBINS, MICHAEL BISHOP, ANDREW A. YOUNG, Durham, NC,
Research Triangle Park, NC
The profound, rapid, and weight-independent antidiabetic effects of
bariatric surgery affirm the promise of modulating gastrointestinal function
for therapeutic purposes. We have previously demonstrated separate glucoselowering effects of inhibitors of the sodium-glucose cotransporter 1 (SGLT1)
and the apical sodium-dependent bile acid transporter (ASBT) in human and/
or animal studies.
A potential synergy between SGLT1 inhibition and ASBT inhibition was
tested in male Zucker-fatty diabetic rats using a novel dose-ratio scanning
method. First, equi-effective (ED30) glucose-lowering doses of an SGLT1
inhibitor (KGA2727; 0.5 mg/kg bid) and an ASBT inhibitor (GSK2299027; 0.14
mg/kg bid) were determined by dose-response analysis of each agent. At high
doses, both KGA2727 and GSK2299027 significantly decreased blood glucose.
In subsequent studies, a maximally effective dose of an ASBT inhibitor
(264W94) reduced plasma [glucose] to 196 В± 33 mg/dL versus 341 В± 24 mg/
dL in vehicle controls. A series of 9 combination treatments in ZDF rats (n=16
rats each), the subtraction of one agent was made up by the addition of the
other, were conducted at the same time. With a 50%-of-ED30 + 50%-of-ED30
mixture (KGA2727, 0.25 mg/kg; GSK2299027, 0.07 mg/kg), maximal effect was
attained (plasma [glucose] 192 В± 29 mg/dL) without evidence of correlated
increases in cecum weight, fecal water content, or fecal bile acid excretion.
In summary, we demonstrate synergy of the glucose-lowering, but not the
adverse effects of distinct gastrointestinal mechanisms (ASBT and SGLT1
inhibition), each capable of being invoked by agents restricted to the gut
lumen.
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174-LB
Low Circulating Levels of Insulin-Like Growth Factor-I (IGF-I) in
Healthy Adult Males Are Associated With Reduced Beta-Cell
Function, Increased Intramyocellular Lipid Content and Enhanced Fat
Utilisation
Adipochip 2.0: Simultaneous Monitoring of Fatty Acid and Glycerol
Secretion from Adipocytes using Microfluidic Enzyme Assays
COLLEEN E. DUGAN, ORMOND MACDOUGALD, ROBERT KENNEDY, Ann Arbor,
MI
AJAY THANKAMONY, DONATELLA CAPALBO, LOREDANA MARCOVECCHIO,
ALSION SLEIGH, LOUISE MCGRATH, ANDERS JUUL, SINE WANDA J�RGENSEN,
ALLAN VAAG, GILES YEO, LES BLUCK, DAVID B. DUNGER, Cambridge, United
Kingdom, Copenhagen, Denmark
Research investigating the mechanisms and functions of adipose tissue
has been spurred in recent years by the growing concern over medical and
economical impacts of the increasing population of individuals living with
obesity-related disorders. Lipolysis is an important metabolic function
of adipocytes that results in the release of fatty acids and glycerol from
triacylglycerol (an energy storage molecule). The physiological energy needs
vary throughout the day, resulting in differing amounts of the released fatty
acids that are recycled back into triacylglycerol or used by peripheral tissues.
Dysfunctional lipolysis and fatty acid recycling are observed in obesityrelated disorders like type 2 diabetes. Our goal is to develop a method of
simultaneously monitoring fatty acid and glycerol concentrations secreted
from the same group of adipocytes to learn more about fatty acid recycling and
adipocyte function. Microfluidics is an ideal platform for perfusing cells and
analyzing secreted products compared to conventional methods because of
its inherent ability to reduce cell and reagent requirements, improve temporal
resolution, and allow automation.
A novel multi-layer PDMS chip has been developed that integrates murine
3T3-L1 adipocyte perfusion, reaction of secreted fatty acid or glycerol with a
fluorescence enzyme assay and detection on one device. The on-line limit of
detection (LOD) of the glycerol assay is 1 ВµM, and the LOD of the fatty acid
assay is 5 ВµM. Adipocytes are cultured on glass coverslips and are transferred
to a reversibly-sealed cell chamber on the chip, where they are perfused for at
least an hour. Secreted fatty acid and glycerol concentrations from adipocytes
are monitored while under basal conditions and during lipolysis stimulation by
the application of isoproterenol.
Low IGF-I levels are linked to increased risk of T2D in epidemiological
studies. We explored fasting metabolism associated with variations in IGF-I
levels in healthy adults.
IGF-I levels were measured in 300 healthy, non-obese male volunteers (age
18-50yr) from a biobank to select 24 subjects (age 34.8В±8.9yr), 12 each in the
lowest (L-IGF) and highest (H-IGF) quartiles of age specific IGF-I SD scores.
The evaluations were undertaken after a 24hr fast, and included glucose
and glycerol appearance rates (Ra) using tracers and an IVGTT to estimate
peripheral insulin sensitivity (IS) and acute insulin and C-peptide responses,
indices of insulin secretion. Other evaluations included magnetic resonance
spectroscopy to measure IMCL, DXA, calorimetry and a muscle biopsy.
The two groups were similar in age and body composition. Fasting glucoses
were similar, however, L-IGF group had reduced levels of insulin (p=0.032) and
C-peptide (p=0.027), and lower glucose Ra adjusted for insulin levels (p=0.027)
suggesting increased hepatic IS. Acute insulin and C-peptide responses
(p<0.05) were lower, however similar peripheral IS resulted in reduced insulin
secretion adjusted for IS (p=0.03) in the L-IGF group. L-IGF group also had
higher overnight levels of free fatty acids (p=0.03) and ОІ-hydroxy butyrates
(p=0.027), increased accumulation of IMCL from 12-24hrs of fast (p=0.008), and
tended to have a lower respiratory quotient (p=0.08) indicating increased fat
utilisation. Furthermore, fat oxidation pathways were upregulated (p=0.001)
while GLUT-1 receptors down-regulated in the muscle on gene expression
array. Overnight Growth Hormone secretion, lipolytic rates and basal metabolic
rates were unchanged.
These data suggests that GF-I levels could be an important marker of ОІ-cell
function and substrate metabolism, and provide new insights into the links
between IGF-I and T2D.
Supported by: NIHR; Cambridge Biomedical Research Centre; BSPED; ACT
For author disclosure information, see page LB66.
ADA-Funded Research
LB45
Integrated Physiology/Obesity
Obesity—Animal
177-LB
Probiotics Improve Glucose Tolerance and Insulin Sensitivity in DIO
Mice via Intestinal Permeability and Microbiota Modulations
175-LB
RENATA A. BAGAROLLI, NATALIA T. DA SILVA, BRUNO M. CARVALHO,
ALEXANDRE G. OLIVEIRA, SARA O. SAAD, MARIO J.A. SAAD, Campinas, Brazil
The Ubiquitin Ligase Siah2 Regulates Inflammatory Gene Expression
in Obesity
Obesity is the main risk factor to the development of insulin resistance and
type 2 diabetes. The common basis among these events is an inflammatory
process characterized by the activation of toll-like receptor 4 (TLR4) by its
main ligand lipopolysaccharide, LPS. Its concentration is higher in obese
people and it is believed that changes in composition of the gut microbiota
and epithelial functions may play a role in the inflammation associated with
obesity. The aim of the study was to evaluate the effects of probiotic on the
insulin sensitivity, TLR4 signaling, intestinal permeability and microbiota
composition in diet-induced obese mice. Male adult Swiss mice composed
randomly 2 groups: chow diet (CTL) and high-fat diet by 5 consecutive weeks
(DIO). During these 5 weeks, some mice of the DIO and CTL groups received
daily a pool of probiotics. Glucose tolerance, insulin signaling (IR, IRS-1, Akt),
TLR4 pathway (TLR4, IKK, JNK, iNOS), gut microbiota and intestinal tight
junctions proteins were evaluated. The DIO animals that received probiotic
presented an expressive improvement in their glucose tolerance test, fasting
glucose and in parallel a significant increase in the phosphorylation levels of
insulin induced IR, IRS1 and Akt in muscle, liver and adipose tissue. There
was a relevant reduction in the TLR4-Myd88 interaction, IKKОІ and JNK
phosphorylation and iNOS expression in DIO mice treated with probiotic. This
treatment also improved the expression of ileal tight-junctions proteins (ZO-1,
Occludin), decreased LPS portal levels and the concentrations of bacteria of
the phylum Firmicutes (associated with obesity) in feces. In conclusion, our
results show that probiotics, through their effects on intestinal permeability
and microbiota composition, can improve insulin sensitivity and signaling of
DIO mice, reducing their inflammation and suggesting potential beneficial
effects in the treatment of insulin resistance and type 2 diabetes.
ELIZABETH FLOYD, GAIL KILROY, LAUREN CARTER, HEATHER KIRK-BALLARD,
SUJOY GHOSH, Baton Rouge, LA
Obesity is a major risk factor for developing insulin resistance and type 2
diabetes and the chronic low-grade inflammation associated with obesity is
an important link in the relationship between obesity and type 2 diabetes.
Adipogenesis depends on the peroxisome proliferator-activated receptor
gamma (PPARγ), a protein that functions as the “master switch” in regulating
lipid and carbohydrate metabolism in adipocytes. The insulin-sensitizing
thiazolidinediones are PPARОі ligands that have potent anti-inflammatory
effects, but are associated with adverse effects that limit their use. In our
studies to understand how PPARОі activity is regulated by posttranslational
modification of PPARОі by ubiquitin, we identified the mammalian homolog
of Drosophilia seven-in-absentia, Siah2, as a regulator of ligand-mediated
changes in PPARОі activity and protein levels in adipocytes. Our current studies
in Siah2 -/- mice indicate Siah2 plays a role in the relationship between obesity
and inflammation of adipose tissue. Siah2 -/- mice become obese on a high-fat
diet and although the adipocytes are uniformly large, there are significantly
fewer “crown-like” structures in the adipose tissue compared to wild-type
mice. This correlates with increased levels of PPARОі protein in adipose tissue
and improved insulin sensitivity as determined by glucose and insulin tolerance
testing and lipolysis assay of isolated adipocytes, suggesting Siah2 is an
important determinant of insulin sensitivity in obesity. Microarray analysis
of the adipose tissue from high-fat fed wild-type and Siah2 -/- mice shows
Siah2 regulates the expression of over 100 genes involved in inflammatory
processes. Genes encoding adipocyte-secreted pro-inflammatory proteins
such as serpine-1 (PAI-1) and serum amyloid A3 (Saa-3) are significantly downregulated in both visceral and subcutaneous adipose depots, identifying Siah2
as modulating obesity-related inflammation in adipose tissue via regulation of
adipocyte biology.
178-LB
ACAM (Adipocyte Adhesion Molecule)/CLMP Inhibits Adipocyte
Hypertrophy in Obesity
Supported by: NIH (R56DK089020)
KAZUTOSHI MURAKAMI, JUN WADA, JUN EGUCHI, DAISUKE OGAWA, ATSUKO
NAKATSUKA, TAKAHIRO TERAMI, NAOTO TERAMI, HIROFUMI MAKINO,
Okayama, Japan
176-LB
Deletion of ABHD6 in Mice Protects from Diet-Induced Obesity, HyperВ­
glycemia and Insulin Resistance, and Enhances Locomotor Activity
We identified adipocyte adhesion molecule (ACAM) / CLMP which
belongs to cortical thymocyte marker in Xenopus (CTX) gene family. ACAM is
predominantly expressed in white adipose tissues and up-regulated in obese
rodents and human subjects with obesity. Two immunoglobulin-like domains
exist in extracellular segment and they are involved in the adhesion process
and homophilic aggregation of the cells (Biochemical J 2005). To explore the
functional role of ACAM in obesity and type 2 diabetes, we generated ACAM
transgenic (Tg) mice under aP2 promoter. Under high fat high sucrose diet, the
increase in body weight was significantly ameliorated in Tg mice compared
with wild type (WT) mice. The fat pad weight and adipocyte size in Tg mice
were reduced. In glucose tolerance and insulin sensitivity tests, plasma
glucose levels were significantly lower in Tg mice. The oxygen consumption
rate was significantly higher in Tg mice and lipid droplets in brown adipose
tissues were prominently depleted. Thus, we investigated mRNA expression
of UCP-1 and PGC1О± and they were significantly up-regulated in ACAM Tg
mice compared with WT mice. To further give insights into the mechanism for
the reduction of lipid accumulation in adipose tissues, we investigated the role
of ACAM in differentiation of 3T3-L1 cells. ACAM is differentially expressed
during the maturation of 3T3-L1 adipocytes; it has two expression peaks at 6
hrs and 10 days after hormonal induction. We identified that KLF4 and CEBP/ОІ
up-regulate the transcriptional activity of ACAM revealed by luciferase assay
using pGL3 vector and the knockdown of ACAM mRNA inhibits mitotic clonal
expansion and lipid accumulation. Finally, we identified myosin II-A and
Оі-actin as interacting proteins forming protein complexes with ACAM by
tandem-affinity purification method. Taken together, the adhesion process and
cytoskeletal organization mediated by ACAM may have an inhibitory role in
adipocyte hypertrophy and lipid accumulation in obesity.
SHANGANG ZHAO, YVES MUGABO, JOSÉ IGLESIAS, RAPHAËL PRENTKI,
JOHANE MORIN, MARIE-LINE PEYOT, ERIK JOLY, MURTHY MADIRAJU, MARC
PRENTKI, Montreal, QC, Canada
Lipogenesis and lipolysis, two essential components of glycerolipid/
free fatty acid cycling, play an important role in regulating insulin secretion
and sensitivity. In the pancreatic ОІ-cells, which have very low levels of
monoacylglycerol (MAG) lipase, MAG hydrolysis is conducted mostly by
membrane bound О±/ОІ-domain hydrolase-6 (ABHD6). We have recently found
that MAG levels increase in ОІ-cells upon suppression of ABHD6 activity both
in vitro and in vivo, associated with enhanced glucose stimulated insulin
secretion, suggesting that MAG is a metabolic coupling factor in glucose
induced insulin secretion.
ABHD6 KO male mice on chow diet grow normally and did not show difference
in food intake, body weight gain, glucose tolerance and insulin sensitivity over
a span of 26 weeks age. Female mice on chow diet show reduced body weight
gain and improved glucose tolerance and insulin sensitivity. However, when fed
with high fat diet for 8 weeks, both male and female ABHD6-KO mice showed
reduction in food intake, body weight gain, insulinemia and glycemia, improved
glucose tolerance and insulin sensitivity, as compared to corresponding wild
type mice. Metabolic studies indicated that ABHD6-KO mice show increased
O2 consumption and thermogenesis, with elevated respiratory exchange ratio
and enhanced locomotor activity. Overall the phenotype in female mice was
more pronounced. In conclusion, ABHD6 KO mice on a high fat diet show a
unique phenotype with enhanced glucose homeostasis, associated with
reduced appetite, body weight gain, as well as increased thermogenesis and
physical activity. Collectively, these results identify ABHD6 as a novel target
for metabolic syndrome, obesity and diabetes.
Supported by: CIHR
For author disclosure information, see page LB66.
ADA-Funded Research
LB46
Integrated Physiology/Obesity
179-LB
exploring the effects of a high-fat diet on metabolism in AhRKO mice. 6-week
old wild-type, AhR heterozygous and knockout male mice were exposed to a
normal chow diet (NCD, 10% fat diet) or a high-fat diet (HFD, 60% fat diet)
for 14 weeks. AhR deficiency inhibited HFD-induced obesity, hepatic steatosis
and insulin resistance, which resulted from increased energy expenditure,
increased PPARОі, adiponectin and leptin expression, decreased inflammation
and enhancement insulin receptor substrate 1 and 2 (IRS1 and IRS2) expression
and insulin-induced Akt phosphorylation in adipose tissue, liver and muscle.
Mechanistically, the metabolic benefits of AhR deficiency were related to the
inhibition of c-Jun N-terminal kinase (JNK) activation and nuclear factor-ОєB
(NF-ОєB) pathway. These findings demonstrate an important role for the AhR in
obesity and insulin resistance, and the AhR signaling pathway may become a
potential therapeutic target. In future, AhR antagonists may be developed to
prevent and treat obesity and type 2 diabetes.
Pro-Inflammatory Effects of Central Leptin on Adipose Tissue Are
Abolished by Adrenergic Denervation
KEHAO ZHANG, JULIE CHEN, WEIJIE LI, CECILIA DAVIS, YANG ZHANG, XINYUAN
DONG, BING LIU, GARY SCHWARTZ, ROGER GUTIERREZ-JUAREZ, MEREDITH
HAWKINS, Bronx, NY
Obesity is characterized by infiltration of adipose tissue by macrophages
and other inflammatory cells.The fat-derived cytokine leptin, whose levels are
increased in obesity, activates immune cells. We previously showed that central
leptin administration rapidly induced adipose inflammation (~2-fold increase in
cytokine expression) and activation of adipose tissue macrophages (ATM) in
normal rats. These effects persisted with high fat feeding, despite resistance
to leptin’s effects on energy balance, suggesting that leptin could fuel adipose
inflammation in obesity (Endocrine Reviews 2011 32:3). To confirm that central
leptin caused adipose inflammation via neural inputs to fat pads, we examined the
impact of perirenal denervation on leptin’s ability to induce adipose inflammation.
Selective, unilateral disruption of adrenergic signaling to perirenal fat pads was
performed in n=16 normal male Sprague Dawley rats (age=10 weeks, weight
~350 g) using multiple injections of 6-OH-dopamine (8mg/ml), with contralateral
perirenal saline injections. The effects of intracerebroventricular leptin 0.25 Ојg/h
(n=8) vs. vehicle (n=8) infusion on adipose tissue inflammation were compared
in the denervated vs. sham-injected fat pads. Denervation of perirenal fat pads
diminished the leptin-induced adipose tissue inflammation, with decreased
expression of TNF-a, IL-6 and iNOS by 38% (p=0.036), 45% (p=0.035) and 32%
(p=0.042), respectively, and with corresponding 39% (p=0.039), 37% (p=0.045) and
28% (p=0.057) reductions in the expression of these cytokines by ATM’s. Thus,
central leptin administration rapidly induces inflammation and ATM activation in
perirenal adipose tissue of rats, and selective adrenergic denervation abolished
the stimulatory effects of leptin on adipose inflammation. Increased leptin
production could contribute to activation of adipose macrophages with weight
gain, thereby exacerbating the metabolic and inflammatory consequences of
obesity.
Supported by: NIH (ES017774)
182-LB
Dietary Methionine Restriction Induces Weight-Loss, Promotes Insulin
Sensitivity and Decreases Adipose Tissue Macrophage Accumulation
in Diet-Induced Obese Mice
GENE P. ABLES, MARK PEFFERS, HEIDI SEYMOUR, INES AUGIE, CARMEN
PERRONE, DAVID ORENTREICH, NORMAN ORENTREICH, Cold Spring, NY
Methionine restriction (MR) in rodent models extends lifespan and induces
favorable metabolic changes on glucose metabolism with a concomitant
reduction in adipose tissue mass. Since the recruitment of adipose tissue
macrophages is implicated in obesity and insulin resistance, we hypothesized
that the MR diet reduces the accumulation of adipose tissue macrophages
which consequently attenuates obesity and insulin resistance.
Diet-induced obese (DIO) C57Bl/6J mice were fed isocaloric high-fat control
(HFD - CF /0.86% methionine) or methionine restricted (HFD - MR/0.12%
methionine) diets containing 60% fat for 12 weeks. The HFD - MR mice had
decreased body weight despite increased food consumption and energy intake
compared to HFD - CF mice. Plasma amino acid analysis by ultra-performance
liquid chromatography (UPLC) assay showed that HFD - MR mice had
decreased concentrations of methionine, cysteine, taurine and lysine, while
glycine, proline, serine, tyrosine and threonine were increased compared to
the HFD - CF. The decreased methionine in the diet lowered fasting blood
glucose, plasma insulin, leptin, PAI1 and resistin concentrations suggesting
increased insulin sensitivity in the HFD - MR mice, which was confirmed in
glucose and insulin tolerance tests. Perigonadal (PGAT), subcutaneous (SCAT)
and brown adipose tissue (BAT) mass were significantly reduced in the HFD MR mice due to increased lipolysis as shown by an increase in free fatty acid
(FFA) levels following an overnight fast. Finally, immunohistochemistry staining
of the perigonadal adipose tissue for the macrophage marker, F4/80, showed
decreased macrophage content in HFD - MR mice fat depots. Taken together,
these data suggest that dietary MR in obese mice could induce weight loss
and attenuate insulin resistance due to reduced accumulation of adipose
tissue macrophages.
180-LB
Simulating Rapid Gastric Emptying With Duodenal Nutrient Infusions
Results in Decreased Food Intake and Reduced Weight Gain
BHUSHAN V. KULKARNI, SONIA LIPP, DARLEEN A. SANDOVAL, ADAM P.
CHAMBERS, DAVID A. D’ALESSIO, STEPHEN C. WOODS, RANDY J. SEELEY,
Cincinnati, OH
Decreased caloric intake contributes to weight loss occurring soon after
some bariatric surgical procedures. We asked whether rapid gastric emptying
following vertical sleeve gastrectomy (VSG) and gastric bypass bariatric
procedures contributes to early satiation and subsequent weight loss. To
simulate rapid gastric emptying, 8 male Long-Evans rats received a duodenal
catheter (DC) and another 8 rats received a similar catheter but placed in
the gastric compartment (GC). Each time rats consumed Ensure Plus from an
available sipper tube, a 50% diluted Ensure Plus was infused via the catheter
into either the duodenum or stomach. The start and end point of infusion
coincided with the start and end point of the ad-lib meal. Over 3 weeks of
these infusions, DC rats exhibited early satiation in the form of decrease in
meal size resulting in significant decrease in daily total caloric intake (oral
plus infusion calories) and significantly reduced total body weight (-10%) as
compared to the GC rats receiving the same infusions into the stomach. NMR
body composition analysis demonstrated that the weight loss in DC rats was
due to decrease in adiposity and not in lean mass. This study suggests that
simulating rapid gastric emptying is sufficient to produce reduced meal size
and cause weight loss. These data suggest that rapid gastric emptying seen
after some bariatric surgical procedures may be important to the observed
reduction in food intake and body weight.
Supported by: Orentreich Foundation for the Advancement of Science
183-LB
Interferon Regulatory Factor 4 Regulates Obesity-Induced Inflammation
Through Regulation of Adipose Tissue Macrophage Polarization
JUN EGUCHI, JUN WADA, HIROFUMI MAKINO, ROSEN D. ROSEN, Okayama,
Japan, Boston, MA
Interferon regulatory factors (IRFs) play functionally diverse roles in the
transcriptional regulation of the immune system. We have previously shown
that several IRFs are regulators of adipogenesis, and that IRF4 is a critical
transcriptional regulator of adipocyte lipid handling. However, the functional
role of IRF4 in adipose tissue macrophages (ATMs) remains unclear, despite
high expression there. Here we show that IRF4 expression is regulated in both
primary macrophages and ATMs of high-fat diet-induced obese mice. Irf4-/macrophages produce higher levels of proinflammatory cytokines, including
IL-1ОІ and TNFО±, in response to fatty acids. In co-culture experiments, IRF4
deletion in macrophages leads to reduced insulin signaling and glucose uptake
in 3T3-L1 adipocytes. To determine the macrophage-specific function of IRF4
in the context of obesity, we generated myeloid cell-specific IRF4 knockout
(MI4KO) mice. MI4KO mice develop significant insulin resistance on high fat
diet despite no difference in adiposity. This phenotype is associated with
increased expression of inflammatory genes and decreased insulin signaling
in adipose tissue, skeletal muscle, and liver. Furthermore, Irf4-/- ATMs express
markers suggestive of enhanced M1 polarization. These findings indicate that
IRF4 is a negative regulator of inflammation in diet-induced obesity, in part
through regulation of macrophage polarization.
Supported by: NIH/NIDDK; Ethicon Endo-Surgery, Inc.
181-LB
Aryl Hydrocarbon Receptor Deficiency Attenuates Diet-Induced
Obesity and Insulin Resistance in Mice
CAN-XIN XU, CHUN WANG, CASSIE JAEGER, STACEY KRAGER, KATHLEEN
BOTTUM, SHELLEY TISCHKAU, Springfield, IL
The aryl hydrocarbon receptor (AhR), together with its partner AhR nuclear
transloacator (ARNT), has been explored extensively for its role in xenobiotic
metabolism. AhR is implicated in xenobiotic-induced insulin resistance
and type 2 diabetes. Our previous study has shown that AhR knockout mice
display decreased peroxisome proliferator activated receptor alpha (PPARО±)
expression, improved glucose tolerance and insulin sensitivity on normal chow
diet. Since “Western diet” is implicated in the development of obesity and
diabetes, we sought to further define the role of AhR in energy homeostasis by
Supported by: NIH (R01DK63906), (R01DK085171)
For author disclosure information, see page LB66.
ADA-Funded Research
LB47
Integrated Physiology/Obesity
184-LB
feeding circuitry. Emerging evidence suggests that prolylcarboxypeptidase
(PRCP) modulates the anorexic effects of О±-MSH, the endogenous ligand for
melanocortin 4 (MC4) receptors. PRCP-deficient mice have reduced food intake
and a lean phenotype. In contrast, obese diabetic patients have elevated
plasma levels of PRCP, suggesting a potential role for PRCP in diabetes and
obesity. We hypothesized that PRCP contributes to regulation of food intake
and that a novel inhibitor of PRCP (UM8190) would reduce blood glucose levels
in obesity. To test this hypothesis, PRCP expression levels were determined
in three experimental animal models, Zucker Diabetic Fatty rats (ZDF), Zucker
Lean (ZL) rats, and wild type (WT) mice. After 16 weeks, PRCP protein levels
were significantly lower (p<0.05, n=6) in left ventricles and kidneys of ZDF than
in ZL rats (n=5). After 32 weeks, while PRCP protein levels in the kidney of ZDF
rats were higher than in ZL rats (P≤0.005, n=6), PRCP protein levels in the left
ventricle of ZDF were significantly lower than in ZL rats (P≤0.005, n=5). To test
the effect on feeding behavior, UM8190 was infused i.v. in WT mice for 10
days. Food intake was reduced in UM8190 -treated mice compared to vehicle
treated WT mice. Unlike the MC4 receptor agonist melanotan II (MTII), i.v.
infusion of UM8190 in mice did not change heart rate or blood pressure. Our
studies highlight the importance of PRCP in obesity. What remains elusive is the
role of PRCP in diabetes. The details of diabetes-accelerated PRCP expression
regulation in obesity and type 2 diabetes could open new therapeutic avenues
to maintain glycemic control.
Imbalance between Neutrophil Elastase and its Inhibitor О±1Antitrypsin in Obesity Alters Insulin Sensitivity, Inflammation and
Energy Expenditure
VIRGINIE MANSUY-AUBERT, QIONG L. ZHOU, XIANGYANG XIE, ZHENWEI GONG,
JUN-YUAN HUANG, ABDUL R. KHAN, GREGORY AUBERT, KARLA CANDELARIA,
HUI ZHANG, ROBIN LOVELL-BADGE, STEVEN R. SMITH, FAZLI R. AWAN, ZHEN Y.
JIANG, Orlando, FL, Baltimore, MD, London, United Kingdom, Faisalabad, Pakistan
The molecular mechanisms involved in the development of obesity and
related complications remain unclear. Using a quantitative serum proteomic
approach, we identified О±1-antitrypsin (A1AT), a natural inhibitor of neutrophil
elastase (NE), was significantly reduced in obese mice. Further validation
studies demonstrated that both human obese subjects and obese mice have
increased activity of neutrophil elastase (NE) and decreased serum levels
of A1AT. NE null (Ela2-/-) mice were resistant to high fat diet (HFD)-induced
bodyweight gain, insulin resistance, fatty liver, neutrophil and macrophage
infiltration, inflammation and fibrosis in white adipose tissues. Overexpression
of human A1AT also alleviated HFD-induced phenotypes in mice. NE small
molecule inhibitor GW311616A reversed insulin resistance and bodyweight
gain in long term HFD-fed mice, suggesting a potential therapeutic effect.
Compared with wild-type mice, Ela2-/- mice augmented circulating high
molecular weight (HMW) adiponectin levels, phosphorylation of AMPactivated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and fatty acid
oxidation (FAO) in the liver and brown adipose tissue (BAT). These data suggest
a novel link of the A1AT-NE system to the AMPK signaling, FAO, and energy
expenditure axis. Hence, the imbalance between A1AT and NE contributes to
the development of obesity and related inflammation, insulin resistance and
liver steatosis.
187-LB
Variations in Susceptibility to Diet-Induced Obesity Between C57BL6/J
and C56BLKs/J Inbred Mouse Strains
EMILY K. SIMS, MASAYUKI HATANAKA, DAVID L. MORRIS, SARAH A. TERSEY,
TATSUYOSHI M. KONO, ZUNAIRA CHAUDHRY, DAN MOSS, NATALIE STULL,
RAGHAVENDRA G. MIRMIRA, CARMELLA EVANS-MOLINA, Indianapolis, IN
185-LB
Impaired glucose tolerance (IGT) and Type 2 Diabetes (T2D) are polygenic
disorders with complex pathophysiologies; recapitulating them with mouse
models is challenging. Despite 70% genetic homology, C57BL/6J (BL6) and
C57BL/KsJ (BLKS) inbred mouse strains differ in response to diet (DIO)- and
genetic-induced obesity. We hypothesized differences would yield insight into
IGT and T2D susceptibility and treatment responses. To define phenotypes in
response to DIO, male BL6 and BLKS mice (8 wks) were fed normal chow, high
fat diet (HFD; 42% kcal from fat), or HFD supplemented with PIO (20mg/kg/day)
for 16 wks. Body composition, glucose metabolism, ОІ cell function and gene
expression, and energy metabolism were analyzed. As expected, HFD BL6
mice gained weight and visceral adiposity. They were hyperinsulinemic and
insulin resistant with IGT, but did not develop T2D due to compensatory ОІ cell
proliferation. PIO did not attenuate HFD-induced weight gain but did decrease
visceral fat mass, normalize serum insulin, and improve insulin sensitivity
and IGT. Islet microarray revealed that PIO partially reversed changes in gene
expression conferred by HFD. In contrast, BLKS-HFD mice gained less weight
due to decreased consumption and increased activity. Visceral adiposity
increased to a lesser extent; addition of PIO increased total fat but not visceral
fat mass. Despite no significant increase in insulin resistance, HFD BLKS mice
had IGT but no change in serum insulin levels, ОІ cell proliferation, or glucosestimulated insulin secretion. Because of distinct compensatory responses,
both strains avoided HFD-induced T2D. BL6 mice met DIO with increased ОІ cell
proliferation and insulin production; BLKS mice responded by restricting food
intake and increasing activity, limiting weight gain. Differences may reflect
divergent responses of humans to a Western lifestyle and drug therapy and
underscore the careful consideration needed when choosing mouse models of
DIO and T2D treatment.
Exchange Protein Directly Activated by cAMP 1 Plays an Important
Role in ОІ3-Adrenergic Induction of UCP1 in WAT and Thermogenesis
via Regulating Lipolysis
YINGXIAN CHEN, ANDREW C.P. TAI, ALAN K.L. KAI, SIDNEY TAM, KAREN S.L.
LAM, STEPHEN S.M. CHUNG, AIMIN XU, SOOKJA K. CHUNG, Hong Kong, China,
Zhuhai, China
Pharmaceutical enhancement of uncoupling protein1 (UCP1) and thermoВ­
genesis has drawn great interest to counteract obesity. Previously, the
exchange protein directly activated by cAMP 1 (Epac1)-deficient mice showed
less induction of beige cells with a significantly less UCP1 expression in
white adipose tissue (WAT) and lower circulating free fatty acid (FFA) after
chronic CL316,243 (a ОІ3-adrenergic receptor agonist, CL, 1mg/kg/day for 10
days) administration, compared to that of wild type (wt) mice. To further study
the role of Epac1 in ОІ3-adrenergic induction of UCP1 and its function, energy
expenditure and thermogenesis were determined. By indirect calorimetry, the
Epac1-deficient mice showed slightly lower oxygen consumption from 9-16
hours after CL (1mg/kg) administration compared to that of wt mice. By using
rectal thermometer, continuously lower rectal temperature within 30 min
after the ninth dose of CL administration was observed in the Epac1-deficient
mice relative to that of wt mice. These results suggest that in the absence
of Epac1, increase of energy expenditure and thermogenesis induced by ОІ3adrenergic activation are compromised, which could be due to lower FFA and
UCP1 induced by CL in the Epac1-deficent mice. To test whether the reduced
FFA is due to compromised lipolysis, glycerol release from WAT explants
was examined ex vivo. Interestingly, Epac1-deficient WAT explants showed
impaired CL-stimulated glycerol release, indicating that absence of Epac1
diminishes ОІ3-adrenergic receptor mediated lipolysis in WAT. In addition,
Western blot showed that phosphorylation of hormone sensitive lipase at
Ser660 by protein kinase A (PKA) was not different in Epac1-deficient WAT
explants incubated with CL (10uM) for 10 min, compared to that of wt mice.
Taken together, Epac1 plays an important role in ОІ3-adrenergic induction of
UCP1 in WAT and thermogenesis via mediating lipolysis independent of PKA.
Supported by: NIH (5T32DK065549-08 to E.K.S.), K08DK080225, R03DK089147,
R01DK093954
Obesity—Human
188-LB
Supported by: Hong Kong GRF (to S.K.C.)
Beloranib, a Novel Methionine Aminopeptidase 2 (MetAP2) Inhibitor,
Appeared Safe and Showed Dose Responsive Weight Loss Over 12
Weeks in Interim Analysis of Ongoing Phase 2 Trial
186-LB
Prolylcarboxypeptidase Expression Is Altered in Experimental Animal
Models of Obesity
DENNIS D. KIM, JAMES E. VATH, ALICE CHEN, JOANNE MARJASON, JOE
PROIETTO, THOMAS E. HUGHES, Cambridge, MA, Herston, Australia, Heidelberg,
Australia
ZIA SHARIAT-MADAR, TAHMINEH TABRIZIAN, ALEXANDRE A. DA SILVA,
JUSSARA M. DA SILVA, JOHN E. HALL, Jackson, MS
Beloranib is a MetAP2 inhibitor that increases fatty acid oxidation and
reduces hunger. Previous proof of concept studies over 4 weeks showed
~4% weight loss with 1-3 mg subcutaneous (SC) beloranib in obese women.
This is a double-blind, placebo-controlled study to investigate the safety/
tolerability, PK/PD, and metabolic effects of SC beloranib. Obese men and
women were randomized to 0.6 (n=37), 1.2 (n=36), or 2.4 mg (n=34) of SC
For author disclosure information, see page LB66.
Proopiomelanocortin (POMC) neurons possess remarkable ability to regulate
feeding behavior and promote energy expenditure. Activation of POMC neurons
results in the release of alpha-melanocyte-stimulating hormone (О±-MSH) and
beta-endorphin which both inhibit feeding. Despite a detailed description of
the roles of О±-MSH, its mechanisms of regulation remain unknown within the
ADA-Funded Research
LB48
Integrated Physiology/Obesity
beloranib vs. placebo (N=38) twice-weekly for 12wks. Body weight (BW),
sense of hunger, and cardiometabolic biomarkers were measured. Results are
based on pre-specified interim analysis of first 19 patients who completed 12
weeks of treatment duration (n=5, 6, 3, and 5 for 0.6, 1.2, 2.4mg, and placebo,
respectively). Patients were white females (mean age 40.3 yr, BW 101.2 kg,
and BMI 37.9 kg/m2). The most common adverse events (AEs) with higher
incidence during beloranib treatment were sleep disturbance, nausea, and
vomiting (resulting in 2 drop-outs from the 2.4 mg group). There were no severe
AEs, serious AEs, or deaths. There were no clinically significant abnormal
laboratory measures, vitals, or ECG findings. After 12wks, subjects on 0.6, 1.2,
or 2.4mg lost an average (В±SEM) BW of -3.8В±0.8, -6.1В±1.5, and -9.9В±2.3 kg
vs. +1.8В±0.4 kg for placebo (all p<0.005 vs. placebo). Hunger, LDL-c, TG, and
hs-CRP decreased in the beloranib groups vs. placebo. Beloranib treatment
for 12wks was generally well-tolerated by SC administration, resulted in rapid
and sustained clinically meaningful BW loss of up to ~10%, improved sense of
hunger and cardiometabolic risk markers in this interim analysis of an ongoing
Phase 2 study, which is scheduled to be completed by May 2013.
homogenate decreased to a greater extent in the CON group compared to the
EX group (-3.40 VS. 0.10 nmol/g tissue/min, P=0.05), again suggesting a shift
towards CHO oxidation in the CON group and a maintenance/enhanced fatty
acid oxidation in the EX group. Exercise intervention during surgically induced
greater weight loss maintains higher fatty acid oxidation at the level of both
whole body and skeletal muscle.
191-LB
Differential Effects of Inverse Agonists on cAMP and ERK1/2 Signaling
Pathways in Six Naturally Occurring Constitutively Active Mutant
Human Melanocortin-4 Receptors
XIUU-LEI MO, YA-XIONG TAO, Auburn, AL
The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor that
plays an essential role in regulating energy homeostasis. Defects in MC4R
are the most common monogenic form of obesity, with more than 150 distinct
mutations identified in human. In addition to the conventional Gs-stimulated
adenylyl cyclase pathway, it has been recently demonstrated that activation
of mitogen-activated protein kinases, extracellular signal-regulated kinases
1 and 2 (ERK1/2), is involved in MC4R-mediated energy balance. Herein,
we investigated the potential of four MC4R ligands (including the agoutirelated peptide (AgRP), MCL0020, Ipsen 5i and ML00253764), which are
inverse agonists at the Gs-cAMP signaling pathway, to regulate the activity of
phosphorylated ERK1/2 (pERK1/2) in wild type (WT) and six naturally occurring
constitutively active mutant (CAM) MC4Rs. We show that these four inverse
agonists acted as agonists for the ERK1/2 signaling cascade in WT and CAM
MC4Rs. Three mutants (P230L, L250Q and F280L) had significantly increased
pERK1/2 level upon stimulation with all four inverse agonists, with maximal
induction ranging from 1.6 to 4.2 fold. WT and one mutant MC4R (D146N) had
significantly increased pERK1/2 level upon stimulation with AgRP, MCL0020
or ML00253764, but not Ipsen 5i. The pERK1/2 levels of 2 mutants (H76R
and S127L) were significantly increased only upon stimulation with AgRP or
MCL0020. In summary, our studies demonstrated for the first time that the
conventionally identified MC4R inverse agonists exert divergent efficacy on
cAMP and ERK1/2 signaling pathway. These results suggested that there are
multiple activation states of MC4R with ligand-specific and/or mutant-specific
conformations capable of differentially coupling the MC4R to distinct signaling
pathways, adding a new layer of complexity to the MC4R signaling.
189-LB
Rescue of Intracellularly Retained Human Melanocortin-4 Receptor
Mutants
HUI HUANG, YA-XIONG TAO, Auburn, AL
The melanocortin-4 receptor (MC4R) is a critical regulator of energy
homeostasis. Mutations of MC4R gene have been identified as the most common
cause of monogenic obesity. Most of the inactivating mutants are defective in
intracellular forward trafficking. Some of these mutants can activate G proteins
once expressed on the cell surface. In this study, we investigated whether
small molecule MC4R ligands could act as pharmacological chaperones,
promoting the proper folding of intracellularly retained MC4R mutants in
Neuro2A and NIE115 cells. Three MC4R ligands including 2 antagonists (Ipsen
5i and ML00253764) and 1 agonist (THIQ) were studied. Totally 14 human
MC4R mutations were studied, including 10 (N62S, I69R, P78L, C84R, G98R,
Y157S, W174C, P260Q, F261S, and C271Y) that are retained intracellularly,
and 4 (О”88-92, D90N, I102S, and N274S) that are expressed normally on
the cell surface. Cells transiently transfected with the empty vector, WT or
mutant receptors were treated with the small molecules for 24 h, and then the
maximal cAMP production stimulated by 10-6 M NDP-MSH were measured
using radioimmunoassay. The results were similar in the two cell lines studied.
With 10-6 M Ipsen 5i treatment, 7 mutants (N62S, I69R, P78L, C84R, W174C,
P260Q, and C271Y) restored function in cAMP production. With 10-5 M THIQ
treatment, 6 mutants (N62S, P78L, C84R, W174C, P260Q, and C271Y) restored
function in cAMP production in Neuro2A cells and 7 (including I69R) in NIE115
cells. With 10-5 M ML00253764 treatment, 4 mutants (N62S, C84R, W174C,
and C271Y) restored function in cAMP production in Neuro2A cells and 3
(excluding C271Y) in NIE115 cells. None of these small molecules had effect
on the 4 control mutants. In summary, we identified 3 small molecule ligands
that could act as pharmacological chaperones, rescuing intracellularly retained
MC4R mutants in neuronal cells. These results will be useful in research
towards personalized medicine for obese patients carrying MC4R mutations.
Supported by: 1-12-BS212
192-LB
Improvement in Insulin Sensitivity and Beta Cell Function in Severely
Obese Adolescents Following Gastric Bypass Surgery
TOM INGE, STEPHEN BENOIT, TODD JENKINS, RONALD PRIGEON, DEBORAH
ELDER, LAWRENCE M. DOLAN, DAVID A. D’ALESSIO, Cincinnati, OH, Baltimore,
MD
The metabolic changes associated with Roux en Y gastric bypass (RYGB)
have not been previously examined in detail in adolescents. We studied 15
non-diabetic adolescents who underwent serial intravenous glucose tolerance
tests before and after RYGB. Insulin sensitivity (SI) was determined using
Bergman’s minimal model. Insulin secretion was measured as the acute insulin
response to glucose (AIRg) and the disposition index (DI) was computed as
AIRgв€™SI.
Mean age was 17 yr; 66% female, 78% Caucasian. Mean BMI decreased
39% by 1 yr (p<0.01). Mean fasting glucose fell by 11% by 2 weeks (p<0.01),
while fasting insulin normalized by 3 mo. SI increased nearly 3-fold by 1 year
(p<0.01). The acute insulin response to glucose (AIRg) decreased by 59% by 1
year. Taking into account changes in SI, insulin secretion (as DI) doubled by 1
year (p<0.01). Indexed to normal, lean adults, DI increased from the 11th to the
32nd percentile over 1 year (p<0.02).
These data demonstrate that severely obese adolescents have severe
insulin resistance, with high secretory demands to maintain normoglycemia
during glucose challenge. When surgery is used late in the development of
adolescent severe obesity (class III), a significant reduction in BMI is achieved,
but subjects remain severely obese. Postoperatively, SI slowly normalizes,
leading to a significant compensatory improvement in beta cell function,
despite persistence of class II obesity.
Supported by: 1-12-BS212
190-LB
Exercise Following Gastric Bypass Surgery Maintains Higher Fatty
Acid Oxidation
TRACEY WOODLIEF, PAUL M. COEN, NICOLE L. HELBLING, GABRIEL S. DUBIS,
JOSEPH A. HOUMARD, BRET H. GOODPASTER, Pittsburgh, PA, Greenville, NC
Severe obesity has been associated with impaired skeletal muscle fatty
acid oxidation. Although gastric bypass surgery (GPS) is an effective and
increasingly common treatment option for severe obesity, the effects of
regular exercise following GPS on preference for fatty acid oxidation are not
clear. The purpose of the study was to determine the effects of GPS, both
with and without regular exercise, on fatty acid metabolism. Subjects were
recruited 1-3 months post-GPS and completed 6-months of either moderate
structured exercise (EX, n = 26) or GPS only control (CON, n = 45). Percutaneous
biopsies of the vastus lateralis were obtained, before and after the 6-month
interventions. 14-C palmitate oxidation was measured in muscle homogenates.
Resting metabolic rate (RMR) and respiratory quotient (RQ) were determined
by indirect calorimetry. Aerobic capacity (VO2 max) was determined by a
graded exercise test. Cardiorespiratory capacity (VO2) max increased in the
EX group (+160 VS. -25 ml/min, P=0.026). In this subset of completers, the EX
group also lost significantly more weight (-23.9 VS. -18.7 Kg, P=0.05). Resting
RQ increased in the CON group (Pre = 0.74; Post = 0.77; P= 0.03), while not
changing in the EX group ( Pre = 0.74: Post = 0.74, P = 0.97), suggesting a shift
in substrate preference to carbohydrate in the CON group and a maintenance
of higher fatty acid oxidation in the EX group. Palmitate oxidation in muscle
For author disclosure information, see page LB66.
ADA-Funded Research
LB49
Integrated Physiology/Obesity
is the increased expression of glucose regulatory protein (GCKR) brought forth
by the rise in fasting insulin.
1.Stefanovski D, Youn JH, Rees M, Watanabe RM, Ader M, Ionut V, et
al. Estimating hepatic glucokinase activity using a simple model of lactate
kinetics. Diabetes Care. 2012 May;35(5):1015-20.
Metabolic parameters
Timepoint (n)
Baseline (15) 2 weeks (11) 3 months (13) 12 months (15)
Mean +/- SEM Mean +/- SEM Mean +/- SEM Mean +/- SEM
BMI (kg/m2)
63.1 +/- 2.8
59.9 +/- 3.6
50.6 +/- 2.6
38.8 +/- 2.1
Fasting gluocose (mg/dl) 94.1 +/- 2.7
82.8 +/- 1.4
84.1 +/- 2.4
83.1 +/- 1.4
Fasting insulin (pM)
152.7 +/- 22.7 106.3 +/- 12.5
66.1 +/- 7.8
46.8 +/- 3.9
SI (x10-5) x min-1 x pM
1.26 +/- 0.52
1.41 +/- 0.31
1.89 +/- 0.38
4.91 +/- 0.83
AIRg (pM)
979 +/- 116 1,015 +/- 177
651 +/- 65
402 +/- 46
Disposition index
891 +/- 165 1,173 +/- 261 1,163 +/- 239 1,855 +/- 382
Supported by: NCATS
195-LB
Reduced Coenzyme Q10 Content and Redox Status Modification in
Obesity and Adipocyte Hypertrophy
THOMAS GRENIER-LAROUCHE, ANNE GALINIER, LOUIS CASTEILLA, ANDRÉ­
ANNE MICHAUD, ANDRÉ CARPENTIER, ANDRÉ TCHERNOF, Sherbrooke, QC,
Canada, Toulouse, France, Quebec, QC, Canada
Supported by: NIH (R03DK068228)
The development of obesity-related metabolic complications is closely
related to adipose tissue dysfunction. This phenomenon is characterized
by altered lipid metabolism and adipokine secretion as well as chronic
inflammation. Occurrence of oxidative stress in white adipose tissues may
contribute to this phenotype. Coenzyme Q10 (CoQ10) is a lipid molecule playing
a central role in the regulation of reactive oxygen species and cellular oxidative
status.
To study the relevance of CoQ10 content in adipose tissue dysfunction, the
abundance of the oxidized (Q10) and reduced (Q10H2) form of this molecule
were determined in subcutaneous (SCAT) and omental (OAT) adipose tissues
in healthy women (n = 29) with a wide range of body mass index (BMI 21.5 to
53.2 kg/m2). The expression of proinflammatory genes was also measured.
Although CoQ10 levels were similar in these compartments, the redox state
of OAT favored the reduced form while the oxidized form was more abundant
in the SCAT. A negative and non-linear association was observed between
omental content in CoQ10 or Q10H2 and BMI, total body fat mass measured by
dual energy x-ray absorptiometry and computed tomography-assessed visceral
adipose tissue area. A depletion of CoQ10 content in SCAT is also observed in
subjects with higher BMI and SCAT area. Greater omental adipocyte diameter
was associated with lower CoQ10 content while hypertrophy of subcutaneous
adipocytes negatively correlated with Q10H2 level. Although the degree of
obesity did not appear to influence adipose tissues level of Q10, a negative
relationship was observed between SCAT Q10 content and mRNA abundance
of CD68 and cyclooxygenase-1. Also, the mRNA abundance of prostaglandin
E2 receptors type 3 and type 4 (EP4 and EP3) increased in patients with low
levels of CoQ10.
This study confirms that OAT and SCAT adipocyte hypertrophy is closely
related to depletion of CoQ10. This could represent a mechanism contributing
to oxidative stress and adipose tissue dysfunction in obesity.
193-LB
The Metabolically Healthy But Obese Phenotype Is Associated With
Lower Plasma Levels of Persistent Organic Pollutants
MARIE-SOLEIL GAUTHIER, REMI RABASA-LHORET, DENIS PRUD’HOMME, DAWEI
GENG, BERT VAN BAVEL, JEROME RUZZIN, Montreal, QC, Canada, Ottawa, ON,
Canada, Г–rebro, Sweden, Bergen, Norway
Obesity is a major risk factor for the development of insulin resistance (IR)
and type 2 diabetes (T2D). However, a subset of obese individuals does not
develop IR and remain Metabolically Healthy but Obese (MHO). They represent
a distinctive human model to delineate key factors that either contribute to or
prevent the development of metabolic abnormalities without the confounding
effect of differences in body fat mass. In the recent years, exposure to
environmental Persistent Organic Pollutants (POPs) has been shown to cause
IR in rodents and to be associated with increased incidence of T2D in humans.
POPs, such as dioxins, polychlorinated biphenyls (PCBs), and organochlorine
pesticides are highly toxic, lipophylic and resistant to degradation. They thus
accumulate in the environment, food chain and human body. We examined the
plasma levels of various classes of POPs in a cohort of well phenotyped nondiabetic obese patients stratified into MHO (n= 36) or Metabolically Abnormal
Obese (MAO; n=40) according to the results of a euglycemic-hyperinsulinemic
clamp. Despite similar age, BMI, and fat mass, MAO patients had 50% lower
insulin sensitivity, decreased serum levels of HDL-C, and increased levels
of ApoB, triglycerides and hsCRP as compared to MHO subjects (p&lt;0.05).
The plasma levels of all but 5 POPs out of a total of 18 POPs measured
were significantly higher in MAO than in MHO subjects (p&lt;0.05). More
specifically, the levels of octachlorodibenzodioxin and all measured dioxin-like
PCBs (congeners 105, 118, 156, 157 and 189) were higher in MAO than in
MHO subjects (1.4-2.9 fold; p&lt;0.05). MAO patients also had higher levels
of transnonchlordane and several nondioxin-like PCBs (congeners 74, 99, 138,
153, 170, and 194)(1.4-2.0 fold; p&lt;0.05). Overall, this data shows a close link
between higher POPs exposure and the presence of metabolic abnormalities
in obese patients. It also provides potential mechanistic explanations for the
metabolically protected MHO phenotype.
196-LB
Effects of Long Term Administration of Liraglutide on Insulin Uptake,
Body Weight and Hypoglycemia in Type I Diabetes
ANTONIOS LEPOURAS, ANASTASIA LINARDI, NIKOLAOS ALEXANDROPOULOS,
Athens, Greece
194-LB
This study was designed to investigate the effect of administration of
liraglutide to patients with type I diabetes. More specifically, insulin uptake,
weight and lipid profile were investigated.
11 volunteers (8 females, 3 males) received liraglutide with their diabetes
treatment for up to 31 months. Mean age was 45.09 yrs and disease duration
was 22.73 yrs. Mean BMI was 30.96 Kg/m2, mean total cholesterol 195.55 mg/
dL and mean uptake for Slow and rapid acting insulin was 19.83 and 34,55 IU
respectively. Liraglutide was generally well tolerated by all patients.
Average patient TRIM-D total score was 72.5 indicative of well accepted
treatment for diabetes.
All patients reported rare or no episodes of hypoglycemia while on liraglutide
treatment compared to daily or frequent episodes prior to treatment.
Obesity Associated Increase in Fasting Insulin Is Related to Decreased
Hepatic Glucokinase Activity in Women
DARKO STEFANOVSKI, RUCHI MATHUR, RICHARD N. BERGMAN, Los Angeles,
CA
Glucokinase (GCK) acts as a component of the “glucose sensor” in pancreatic
ОІ-cells and possibly in other tissues, including the brain. However, >99% of
GCK in the body is located in the liver, where it serves as a “gatekeeper”,
determining the rate of hepatic glucose phosphorylation. Specific to the liver,
as major end product of GCK is lactate, which can be measured as a surrogate
for GCK activity. Recently, we introduced a novel model of lactate kinetics (1),
during the frequently-sampled intravenous glucose tolerance test (FSIGT) to
estimate in vivo hepatic glucokinase (GCK) activity (KGK), glycolysis (K12) and
whole body lactate clearance (K01). While the FSIGT is a gold standard, it is
difficult to do in the clinical setting. The oral glucose tolerance test (OGTT)
is more practical for the clinical assessment of glucose homeostasis. Our
objective was to estimate the hepatic indices from OGTT glucose and lactate
data in 20 Caucasian non-diabetic females (age: 31В±1, BMI: 26.9В±1.2). Once
consented, Participants underwent a 72 hr carbohydrate load, followed by a
standard 75g oral glucose tolerance test performed at our General Clinical
Research Center. The model was uniquely identifiable in all 20 subjects.
Estimates of GCK activity are inversely correlated to fasting insulin (r=-.59,
P=.01), and percent body fat as calculated by BAI index (r=-.54; P=.02).
In conclusion, we show that in women, hepatic GCK activity is incrementally
decreased with the increase in percent body fat and the subsequent rise in
fasting insulin. One possible mechanism linking the decrease in GCK activity
Weight
BMI
Total Cholesterol
LDL
Triglycerides
Slow Insulin
Fast Insulin
Average Change
-7,70
-3,37
-21,00
-26,50
6,29
0,40
-10,00
Average % Change
-9,40%
-11,64%
-11,09%
-22,63%
6,57%
1,33%
-54,95%
Administration of liraglutide resulted in significant weight reduction both
in terms of absolute weight and in terms of BMI. The lipid profile of patients
also improved with reductions in total cholesterol and LDL, while HDL and
triglycerides do not appear to be decreased. Insulin uptake was significantly
For author disclosure information, see page LB66.
ADA-Funded Research
LB50
Islet Biology/Insulin Secretion
reduced for all patients for rapid-acting insulin, while slow insulin remained at
the same levels. From these early results it appears that the administration of
liraglutide in patients with type I diabetes can be beneficial in weight control
as well as reduced uptake of insulin with marked decrease in incidences of
hypoglycemia in spite of the weight loss.
similar effect on visceral adipose tissue from lean and morbidly obese subjects
with respect to the gene expression of adipogenic markers.
Supported by: ISCIII (PI11/01661); CES (10/004); CIBERobn; Education Ministry
(AP2009-453)
199-LB
197-LB
Withdrawn
Two-Year Outcomes of a Randomized Controlled Trial of Behavioral
Treatment for Comorbid Obesity and Depression in Women
SHERRY PAGOTO, KRISTIN L. SCHNEIDER, BRAD APPELHANS, MOLLY WARING,
MATTHEW C. WHITED, ANDREW M. BUSCH, JESSICA OLESKI, PHILIP MERRIAM,
YUNSHENG MA, BARBARA OLENDZKI, STEPHENIE C. LEMON, IRA S. OCKENE,
SYBIL CRAWFORD, Worcester, MA, Chicago, IL, Greenville, NC, Providence, RI
The co-occurrence of obesity and depression is problematic given that each
contributes to risk for type 2 diabetes. Patients often prioritize weight loss
over depression, but data show that weight loss outcomes are poor in people
with depression. The purpose of this study was to compare two approaches to
treating co-occurring obesity and depression, one that addresses depression
prior to weight, and another that addresses weight only. Two-year outcomes
are reported. Obese women with major depressive disorder (N=161, mean
age=45.9, SD=10.8) were randomized to one of two 6-month interventions.
In one condition, 10 weeks were devoted to behavior therapy for depression
and then a 16 week lifestyle intervention (BA) was initiated at week 8. In the
other condition all 24 weeks were devoted to a lifestyle intervention (LI). We
hypothesized that devoting treatment time to depression will improve both
weight and depression outcomes. Main outcome measures included weight
and depression remission. Results. Intention-to-treat analyses revealed both
conditions lost significant weight, but no differences were observed between
conditions at 6-months (BA= -3.0%, SE= - 0.65%; LI= -3.7%, SE = 0.63%; p =
0.48), 1-year (BA= -2.6%, SE= 0.77%; LI= -3.1%, SE=0.74%; p= 0.72), or 2-years
(BA= -0.8%, SE= 1.10%; LI= -2.5%, SE=1.00%; p= 0.26). The BA condition
evidenced significantly higher depression remission rates relative to the LI
condition at 6-months (BA = 60.7%; LI =39.6%, p=.01), 1-year (BA =66.4%;
LI =47.4%; p =.03), and 2-years (BA =73.8%; LI =55.9%, p=.03). Conclusion.
Devoting treatment time to depression does not compromise or enhance
weight loss but improves depression significantly. Although weight rebounded
at 2 years, depression remission rates continued to rise. Behavior therapy for
depression appears to have long lasting effects on mood and may be a helpful
first step in treatment for women with depression and obesity.
Islet Biology—Apoptosis
200-LB
Reporter Protein Complementation System Identifies Pterostilbene as
Nrf2 Activator and Protects Pancreatic ОІ-Cells Against Apoptosis
RAMASAMY PAULMURUGAN, KUNKA MOHANRAM RAMKUMAR, THILLAI V.
SEKAR, KIRA FOYGEL, BHAKKIYALAKSHMI ELANGO, Palo Alto, CA, Kattankulathur,
India
Nrf2 (Nuclear factor erythroid 2 Related factor 2), a “master regulator”
of cell survival, modulates the expression of phase II metabolic enzymes
and antioxidant genes for maintaining cellular homeostasis. Under normal
conditions, Nrf2 is associated with its inhibitor Keap1 (Kelch-like ECH
associated protein 1) which, upon activation, translocates into the nucleus
and triggers antioxidant response through Antioxidant Responsive Element
(ARE). Thus, Nrf2 activation through ligands is a promising approach for
combating oxidative stress-mediated disorders, including diabetes. We
described a cell-based luciferase enzyme fragment complementation (EFC)
assay to identify potent Nrf2 activators, based on specific interaction of Nrf2
and Keap1. In order to study the mechanism of Nrf2 activation by molecular
imaging, CLuc-Nrf2 and NLuc-Keap1 constructs that showed maximum level of
complement dissociation signal were used to develop HEK293T cell stably coexpressing the fusion proteins. Among the several Nrf2 activators screened,
pterostilbene (PTS), a naturally available stilbene compound, showed effective
Nrf2 activation, as observed by luminometric screening and validation in a
high throughput-screening platform. Follow-up studies were focused on PTS
to reveal its mechanistic role in hyperglycemia. PTS reduced hyperglycemiainduced ROS formation, and also prevented mitochondrial and nuclear DNA
damage in INS-1E cells. PTS increased the expression of Nrf2 downstream
target genes such as Heme Oxygenase 1, NADPH: Quinone Oxidoreductase
1, Glutathione S-transferase, as revealed by qRT-PCR, which was further
confirmed using luciferase reporter driven by ARENQO1 and GST1 promoters.
These findings may improve the understanding of mechanisms mediating antiapoptotic effects of PTS on pancreatic ОІ-cells, and will also form the basis for
its potential use as a therapeutic agent in diabetes management.
Supported by: NIMH (R01MH078012)
198-LB
Effect of 1, 25-Dihydroxyvitamin D3 on VDR Gene Expression and AdiВ­
poВ­genesis in Human Adipose Tissue
MERCEDES CLEMENTE-POSTIGO, ARACELI MUГ‘OZ-GARACH, LOURDES
GARRIDO-SANCHEZ, ROSA BERNAL-LOPEZ, INMACULADA MORENO-SANTOS,
DANIEL CASTELLANO-CASTILLO, DIEGO FERNANDEZ-GARCIA, FERNANDO
CARDONA, FRANCISCO J. TINAHONES, MANUEL MACIAS-GONZALEZ, MГЎlaga,
Spain, Tarragona, Spain
Supported by: SRM University; Stanford University
Vitamin D has been associated to obesity. Vitamin D exerts its action by
means of the vitamin D receptor (VDR) which forms a heterodimer with the
retinoic acid X receptor (RXR), acting as transcription factor of a number of
genes. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3, the active form of vitamin
D) up-regulates VDR gene expression and inhibits adipogenesis in 3T3-L1
preadipocytes. By contrast, 1,25(OH)2D3 promotes the differentiation of
human and mouse preadipocytes. Moreover, it has been reported a higher
adipose tissue VDR gene expression in obese patients than in lean subjects,
which suggests a differential vitamin D dynamics in adipose tissue according
to the obesity degree. Thus, the aim of this study was to analyze the effect of
1,25(OH)2D3 on the gene expression of VDR, RXRО± and adipogenic markers in
human adipose tissue from lean and from morbidly obese subjects.
Visceral adipose tissue explants from morbidly obese (ATMO) and lean (ATL)
donors were cultured and undergone to a range of 1,25(OH)2D3 concentrations
(10-6 M, 10-7 M, 10-8 M). Gene expression of VDR, RXRО± and adipogenic
markers (PPARОі, C/EBPО±, SREBP1 and aP2) was measured.
VDR gene expression was significantly higher in ATMO than in ATL.
1,25(OH)2D3 significantly increased VDR gene expression in ATMO, but had no
effect on VDR gene expression in ATL. No significant effects of 1,25(OH)2D3
in ATMO or ATL was seen on the gene expression of RXRО± or the adipogenic
markers analyzed, although a trend towards lower mRNA levels of C/EBPО± and
aP2 after stimulation with 1,25(OH)2D3 (10-6M) was observed in both ATMO
and ATL.
There is a different VDR gene expression response to 1,25(OH)2D3 in visceral
adipose tissue according to the obesity degree. By contrast, 1,25(OH)2D3 has a
The Transcriptome of Metabolically Stressed Human Islets
201-LB
MIRIAM CNOP, GUY BOTTU, THASSO GRIEBEL, BAROJ ABDULKARIM, LORELLA
MARSELLI, PIERO MARCHETTI, MARK I. MCCARTHY, MICHAEL SAMMETH,
DECIO L. EIZIRIK, Brussels, Belgium, Barcelona, Spain, Pisa, Italy, Oxford, United
Kingdom, Petropolis, Brazil
Pancreatic ОІ cell dysfunction and death are central in the pathogenesis of
type 2 diabetes (T2D). Saturated free fatty acids cause metabolic stress and
contribute to ОІ cell failure. Here we profiled the transcriptome of human islets
exposed to palmitate to map mechanisms of ОІ cell demise.
Using RNA-sequencing we identified transcripts of 5 human islet
preparations, basally or following 48 h palmitate exposure (0.5 mM, 1%
BSA). Organ donors were aged 55В±9 years. Islet ОІ cell purity by insulin
immunostaining was 50В±5%. Samples were sequenced on Illumina Genome
Analyzer II and data analyzed using GEM mapper and Flux Capacitor. Transcript
expression was considered changed by Benjamini-Hochberg-corrected Fisher
tests (p<0.05) and if modified in the same direction in ≥4/5 samples. Genes
were annotated manually or using Ingenuity Pathway Analysis (IPA) or DAVID.
Human islets expressed 30,026 transcripts corresponding to 19,882 genes.
Palmitate induced 428 genes and downregulated 897 genes, including genes
regulating the endoplasmic reticulum (ER) stress response, ubiquitin and
proteasome function, autophagy and apoptosis. Transcripts related to innate
immunity were upregulated and several HLA transcripts downregulated.
Several transcription factors controlling ОІ cell phenotype were inhibited,
including PDX1 and GATA6, which is now functionally studied. 52/63 of the T2D
For author disclosure information, see page LB66.
ADA-Funded Research
LB51
Islet Biology/Insulin Secretion
204-LB
candidate genes were expressed with an RPKM ≥1, and palmitate modified
expression of 11 of these. Palmitate caused a shift in alternative splicing in
574 transcripts. IPA confirmed that top changed functions related to cell death
and cell development. DAVID analysis of transcription factor binding sites in
palmitate-modified genes pointed to a role for XBP1 and ATF6, mediating the
ER stress response.
In conclusion, we used RNA-sequencing to map the human islet
transcriptome and identified novel mechanisms of palmitate-induced ОІ cell
dysfunction and death. The data point to crosstalk between metabolic stress
and T2D candidate genes at the ОІ cell level.
mTOR Signaling Contributes to Developmental Programming of PanВ­
creatic Beta-Cell
EMILYN ALEJANDRO, BRIGID GREGG, TAYLOR WALLEN, DANIEL MEISTER, DOGA
KUMUSOGLU, ANGELA CHEN, MATTHEW MERRINS, LESLIE SATIN, ERNESTO
BERNAL-MIZRACHI, Ann Arbor, MI
Nutrients and growth factors converge on mTOR, which is involved in the
regulation of growth and development of many organs including the pancreas.
We hypothesize that mTOR plays a role on ОІ-cell during fetal development. To
develop a mouse model of maternal low-protein, pregnant C57BL/6 mice were
fed control or low-protein diet throughout (LP0.5) pregnancy. We examined
islet morphology in newborns and metabolic studies on LP0.5 offspring during
adulthood. Rescue experiments to assess the involvement of mTOR was
studied in LP0.5 offspring with transient gain of mTOR complex 1 function. A
significant decrease in insulin levels and ОІ-cell fraction in LP0.5 newborns was
observed. These changes were associated with reduced phosphorylation of
Ribosomal protein S6 in islets of LP0.5 offspring, suggesting that LP treatment
had a negative impact on mTOR signaling and that this pathway could be
involved in this process. Adult LP0.5 showed glucose intolerance despite
enhanced insulin sensitivity, which points to a primary defect at the ОІ-cell
level. Indeed, glucose-induced insulin secretion from LP0.5 islets was blunted.
KCl-induced insulin secretion was reduced, implying a defect that was distal
to Ca2+ influx in LP0.5 islets. Reduced Insulin2 expression and insulin total
content were associated with down-regulation of Pdx-1 message and total
protein in LP0.5 islets. A significant reduction in mTOR protein, specifically in
LP0.5 islets, was observed. The normalization of the ОІ-cell mass defect by gain
of mTORC1 function was explained at least in part by enhanced proliferation.
ОІ-cell over-expression of Rheb transiently during the last week of development
was sufficient to rescue the impairment in glucose tolerance in adult LP0.5
mice. These data suggest that nutrient environment during fetal life programs
glucose homeostasis by inducing permanent changes on mTOR expression
and signaling. In addition, these experiments underscore a novel role of mTOR
signaling in ОІ-cell development and fetal programming.
Supported by: FP7 BETABAT
202-LB
Protective Effect of Nicotinamide on High Glucose/Palmitate-Induced
Glucolipotoxicity to INS-1 Beta Cells Is Attributed to Its Inhibitory
Activity to Sirtuins
SOO JIN LEE, Suwon, Republic of Korea
This study was initiated to determine whether the protective effect of
nicotinamide (NAM) on high glucose/palmitate (HG/PA)-induced INS-1 beta cell
death was due to its role as an anti-oxidant, nicotinamide dinucleotide (NAD+)
precursor, or inhibitor of NAD+-consuming enzymes such as poly (ADP-ribose)
polymerase (PARP) or sirtuins. All anti-oxidants tested were not protective
against HG/PA-induced INS-1 cell death. Direct supplementation of NAD+ or
indirect supplementation through NAD+ salvage or de novo pathway did not
protect the death. Knockdown of the NAD+ salvage pathway enzymes such
as nicotinamide phosphoribosyl transferase or nicotinamide mononucleotide
adenyltransferase did not augment death. On the other hand, pharmacological
inhibition or knockdown of PARP did not affect death. However, sirtinol as
an inhibitor of NAD-dependant deacetylase or knockdown of Sirt3 or Sirt4
significantly reduced the HG/PA-induced death. These data suggest that
protective effect of NAM on beta cell glucolipotoxicity is attributed to its
inhibitory activity on sirtuins.
Supported by: NIH
Islet Biology—Beta Cell—Development and
Postnatal Growth
205-LB
Function of CISH and SOCS2 on Beta-Cell Proliferation During
Pregnancy
203-LB
YANG JIAO, SEBASTIAN RIECK, JOHN LELAY, KLAUS KAESTNER, Philadelphia, PA
Intrapatient Variations in Type 1 Diabetes-Specific Ips Cell DifferentiaВ­
tion Into Insulin-Producing Cells
Prolactin / placental lactogen (PL/PRL) regulate beta-cell proliferation during
pregnancy. After PL/PRL binds to the prolactin-receptor (PRL-R), the receptor
dimerizes, JAK2 kinase is activated and phosphorylates the PRL-R. STAT5
is recruited to phosphorylated PRL-R and is phosphorylated in turn by JAK2.
Phosphorylated STAT5 then dimerizes and translocates into the nucleus to
regulate gene expression as a transcription factor.
A group of known targets of STAT5 is up-regulated during pregnancy,
including Prl-r, Glut-2, and Cyclin D2, resulting in increased beta-cell
proliferation and insulin secretion. Cish and Socs2 are also up-regulated in
mouse islets during pregnancy, forming a negative feedback loop to inhibit
JAK2/ STAT5 signaling, thus potentially limiting proliferation.
SOCS2 and CISH are “Suppressors of the Cytokine Signaling” proteins, a
family of eight members with similar structure. Different gene ablation models
and transgenic mice for multiple Socs genes have been described, and show
various phenotypes depending on which cytokine signal they regulate.
It is unclear whether CISH and SOCS2 limit beta-cell proliferation during
pregnancy. Since lactogen signaling is critical for beta-cell proliferation and
beta-cell function during pregnancy, and Cish, and to a lesser extent Socs2,
are induced during pregnancy, we hypothesized that these two SOCS proteins
negatively regulate beta-cell proliferation and beta-cell function. Here, we
derived a novel mouse model with conditional ablation of the Cish gene in
beta-cells to test the hypothesis that removing this negative feedback inhibitor
could be exploited to stimulate beta-cell replication.
Our findings reveal that: first, Cish deficiency in beta-cells is not sufficient
to increase beta-cell DNA replication during pregnancy, and does not alter
glucose tolerance before, during, or after pregnancy; second, Cish deficiency
does not alter Stat5 signaling; And third, Socs2 might be compensating for
Cish deficiency during pregnancy.
YASUHIRO IKEDA, TAYARAMMA THATAVA, RAMAKRISHNA EDUKULLA, YOGISH
C. KUDVA, Rochester, MN
Nuclear reprogramming of adult somatic tissue enables embryo-independent
generation of autologous, patient-specific induced pluripotent stem (iPS) cells.
Exploiting this emergent regenerative platform for individualized medicine
applications requires the establishment of bioequivalence criteria across
derived pluripotent lines and lineage-specified derivatives. Here, from individual
patients with type 1 diabetes (T1D) multiple human iPS clones were produced
and prospectively screened using a battery of developmental markers to assess
respective differentiation propensity and proficiency in yielding functional
insulin (INS)-producing progeny. Global gene expression profiles, pluripotency
expression patterns, and the capacity to differentiate into SOX17- and FOXA2positive definitive endoderm-like cells were comparable among individual iPS
clones. However, notable intrapatient variation was evident upon further guided
differentiation into HNF4О±- and HNF1ОІ-expressing primitive gut tube, and INSand glucagon-expressing islet-like cells. Differential dynamics of pluripotencyassociated genes and pancreatic lineage-specifying genes underlined clonal
variance. Successful generation of glucose-responsive INS-producing cells
required silencing of stemness programs as well as the induction of stagespecific pancreatic transcription factors. Thus, comprehensive fingerprinting
of individual clones is mandatory to secure homogenous pools amenable for
diagnostic and therapeutic applications of iPS cells from patients with T1D.
We will also present the propensities of iPS cells for pancreatic differentiation
and teratoma formation in immuno-compromised mice.
Supported by: Marriott Awards; Harold E. Eisenberg Foundation; Minnesota
Partnership Grant
Supported by: NIDDK (R01DK055342)
For author disclosure information, see page LB66.
ADA-Funded Research
LB52
Islet Biology/Insulin Secretion
206-LB
Replication and Differentiation Into Insulin-Producing Cells of Human
Adult Pancreatic Duct Cells Exposed to Liraglutide In Vitro
208-LB
A Key Role for Pyruvate Kinase Regulating Insulin Secretion IndeВ­
pendent of Enzymatic Activity
NOELIA TÉLLEZ, MAR PAIRÓ, MONTSERRAT NACHER, PATRICIA SAN JOSÉ TERRÓN,
EDUARD MONTANYA, Barcelona, Spain
REBECCA L. PONGRATZ, XIAOJIAN ZHAO, TIAGO ALVES, ORLANDO YARВ­BORВ­
OUGH, MATTHEW G. VANDER HEIDEN, RICHARD G. KIBBEY, New Haven, CT,
Cambridge, MA
We aimed to investigate whether liraglutide, a human long-acting GLP-1
analogue, could enhance differentiation of human adult pancreatic duct cells into
insulin-producing cells in vitro.
CA19.9+ duct cells were purified by magnetic cell sorting from the exocrine
fraction of pancreas from 12 human cadaveric organ donors (4 male, age
56В±3; BMI 27.8В±1.62). Sorted cells were cultured in suspension for 30 days in
differentiation medium with or without liraglutide (300nM), and/or EGF (20ng/
ml). Gene expression was determined by real time RT-PCR. Replication (BrdU) and
protein expression were analyzed by immunofluorescence. Insulin and c-peptide
were determined by ELISA.
After 2-3 days in culture, the sorted cell population clustered into pancreatoВ­
spheres (92.4В±0.45% duct; 0.19В±0.07% c-peptide+ cells). Gene expression of
krt19 was reduced on days 3, 7 and 30 compared with post-sorting day (p< 0.05).
Duct cell replication remained low along the 30 days of culture with or without
liraglutide. EGF alone and in combination with liraglutide resulted in similar
stimulation of duct cell replication (p< 0.05). Gene expression of ins, sst, gcg and
pdx-1 was similarly increased in liraglutide-treated and non-treated cultures at
day 30 compared with post-sorting day and day 3 (p<0.01). Insulin and c-peptide
content (corrected per DNA) was significantly increased on day 30 compared
with post-sorting day (p<0.05), but remained very low compared with human
islets (≈1%). It was similar in liraglutide-treated and non-treated cultures. Insulin
secretion did not increase in response to glucose stimulation.
These results support the hypothesis that adult human pancreatic duct cells can
differentiate into insulin-producing cells. The GLP-1 analogue liraglutide did not
improve human adult duct cell differentiation into insulin-positive cells, and did
not exert a mitogenic effect in human adult duct cells.
Mitochondria are intimately involved in the signal coupling glucose
metabolism to insulin secretion. Putative mitochondrial metabolic signals
include ATP produced via oxidative metabolism as well as several cataplerotic
metabolic fluxes and cycles. The glycolytic enzyme pyruvate kinase (PK) is
poised to play an essential role either by regulating the concentration of PEP
and/or the availability of pyruvate. Pancreatic beta-cells contain both the
PK-L and the PK-M2 isoforms that are both subject to regulation by allosteric,
transcriptional and post-translational modifications. To determine if metabolic
control is exerted at the PK step, we overexpressed the constitutively active
human muscle isoform (PK-hM1) in INS-1 832/13 cells. In dominant PK-hM1
cells, hM1 message increased to 80% of endogenous PK-M2 message. PK-M2
message declined 31% (P=0.038) while PK-L increased 45% (P=0.0005) and
together with PK-hM1 the total PK activity increased 7-fold. Glucose-stimulated
and uncoupled respiration trended higher as did the ATP concentration. Proximal
mitochondrial metabolites were the same, though malate and fumarate were
reduced. In contrast, both proximal and distal TCA cycle flux (measured
using mass isotopologue multi-ordinate mass spectroscopy) was identical to
controls. Despite having the same total insulin content, ATP content and higher
O2 consumption, glucose-stimulated insulin secretion was reduced >55% in PKhM1 dominant cells (control 316В±10 vs. PK-hM1 141В±7 ng/mL/hr/mg protein,
P=3x10-7). While the cells had indistinguishable tolbutamide-stimulated
insulin release, pyruvate-stimulated insulin secretion was surprisingly reduced
as well (control 87В±7 vs. PK-hM1 58В±6, P=0.011) implicating PK in metabolic
steps distal to pyruvate metabolism. These results suggest that PK-M2 exerts
a positive regulatory influence that can be metabolically separated from total
PK activity and is in keeping with an important role for PEP cycling in insulin
release.
Supported by: ISCIII (PI10/00636); CIBERDEM; Novo Nordisk A/S
Islet Biology—Beta Cell—StimulusSecretion Coupling and Metabolism
209-LB
Clock-Controlled Output Gene Dbp Is a Regulator of Arnt/Hif-1Гџ Gene
Expression in Pancreatic Islet Гџ-Cells
207-LB
HIROKO NAKABAYASHI, YASUHARU OHTA, MASAYOSHI YAMAMOTO, YOSUKE
SUSUKI, AKIHIKO TAGUCHI, KATSUYA TANABE, MANABU KONDO, MASAYUKI
HATANAKA, YUKO NAGAO, YUKIO TANIZAWA, Ube, Japan
Constitutive, Pulsatile Release of Gamma-Aminobutyric Acid CoordiВ­
nates Insulin Secretion in Human Pancreatic Islets
Aryl hydrocarbon receptor nuclear translocator (ARNT) / hypoxia-inducible
factor-1Гџ (HIF1- Гџ) has emerged as a potential determinant of pancreatic
Гџ-cell dysfunction and type 2 diabetes in humans. An 82% reduction in Arnt
expression was observed in islets from type 2 diabetic donors as compared to
non-diabetic donors. However, few regulators of Arnt expression have been
identified. Meanwhile, disruption of the clock components CLOCK and BMAL1
is known to result in hypoinsulinemia and diabetes, but the molecular details
remain unclear. In this study, we identified a novel molecular connection
between Arnt and two clock-controlled output genes, albumin D-element
binding protein (Dbp) and E4 binding protein 4 (E4bp4).
By conducting gene expression studies using the islets of Wfs1-/- Ay/a
mice that develop severe diabetes due to Гџ-cell apoptosis, we demonstrated
clock-related gene expressions to be altered in the diabetic mice. Dbp
mRNA decreased by 50%, E4bp4 mRNA increased by 50%, and Arnt mRNA
decreased by 30% at Zeitgever Time (ZT) 12. Mouse pancreatic islets exhibited
oscillations of clock gene expressions. E4BP4, a D-box negative regulator,
oscillated anti-phase to DBP, a D-box positive regulator. We also found lowamplitude circadian expression of Arnt mRNA, which peaked at ZT4. Overexpression of DBP raised both mRNA and protein levels of ARNT in HEK293
and MIN6 cell lines. Arnt promoter-driven luciferase reporter assay in MIN6
cells revealed that DBP increased Arnt promoter activity by 2.5-fold and that
E4BP4 competitively inhibited its activation. In addition, on ChIP assay, DBP
and E4BP4 directly bound to D-box elements within the Arnt promoter in MIN6
cells. These results suggest that in mouse pancreatic islets mRNA expression
of Arnt fluctuates significantly in a circadian manner and that the downregulation of Dbp and up-regulation E4bp4 contribute to direct suppression of
Arnt expression in diabetes.
DANUSA MENEGAZ, JUDITH T. MOLINA, JOANA ALMACA, RAYNER RODRIGUEZDIAZ, PER-OLOF BERGGREN, ALEJANDRO CAICEDO, Miami, FL
The insulin-secreting beta cell of the pancreatic islet releases the neuroВ­
transmitter gamma-aminobutyric acid (GABA) as a paracrine signal that inhibits
surrounding alpha cells and promotes beta cell survival. It is unclear, however,
how and when GABA is secreted from human islets. Here we show that the
human islet is periodically pervaded by a wave of constitutively released GABA.
This GABA secretion is independent of glucose concentration and does not require
conventional Ca2+-dependent exocytosis but membrane transport of a metabolic
pool of GABA. This secretory activity produces robust periodic GABA pulses that
impose a rhythm on insulin secretion, thus helping increase the synchronicity of
pulsatile insulin secretion. GABA secretion is disrupted in human islets from type
2 diabetic patients, which offers an explanation for the disorganized hormonal
output under diabetic conditions. Our results indicate that loss of GABA release
is due to excessive palmitoylation during hyperlipidemia, which sequesters the
GABA-synthesizing enzyme GAD65 and reduces cytosolic GABA production in
beta cells. Because restoring GABA signaling can be proposed as an intervention
point to promote islet function, our study may have implications for a novel
pharmaceutical strategy for the treatment of diabetes.
Supported by: NIH/NIDDK (R01DK084321)
For author disclosure information, see page LB66.
ADA-Funded Research
LB53
Islet Biology/Insulin Secretion
210-LB
between apoptosis and proliferation of beta cells. GLP-1 appears to inhibit the
apoptosis and stimulate the proliferation of pancreatic beta cells. However, it
has not been evaluated whether GLP-1 may restore beta cell function or islet
mass in the mitochondrial diabetes.
In this study, we have developed the new animal model of beta cell specific
mitochondrial dysfunction by breeding the Crif1flox/flox mice with RIP2-cre mice.
CRIF1 is a protein required for the intramitochondrial production of mtDNAencoded OXPHOS subunits; therefore, CRIF1 deficiency results in specific
failure of OXPHOS capacity.
CRIF1 deficiency in pancreatic beta cells resulted in functional defect of
insulin secretion without decrease of islet beta cell area in 4 week-old mice.
11 week-old mice with beta cell specific CRIF1-deficiency showed diabetic
phenotypes with marked defect of insulin secretion with 70% decreased islet
area. GLP-1 receptor agonist (Exenatide, 10 nM/kg) was given to the beta
cell specific CRIF1 knockout mice (4 week-old) for 4 weeks and measured the
insulin secretion and islet area. The administration of GLP-1 receptor agonist
in wild type mice enhanced insulin secretion and increased islet area (35%)
compared to vehicle group. However, GLP-1 receptor agonist in beta cell
specific CRIF1 knockout mice did not improve the insulin secretion and not
preserve the islet area. Consequently, GLP-1 receptor agonist did not improve
the diabetic phenotypes in mice with beta cell-specific Crif1-deficiency. Based
on these findings, we concluded that short-term treatment of GLP-1 receptor
agonist was not effective to reverse the diabetic phenotypes by preserving
islet mass and insulin secretion in mice model of mitochondrial diabetes with
beta cell specific CRIF1 deficiency.
Critical Role of Actin Dynamics Regulated by N-WASP and Cofilin in
the Biphasic Response of Glucose-Induced Insulin Secretion
TADAO SHIBASAKI, EITAI UENISHI, HARUMI TAKAHASHI, YUTAKA OISO,
SUSUMU SEINO, Kobe, Japan, Nagoya, Japan
Actin dynamics is involved in insulin secretion, but molecular mechanisms
of the regulation of actin dynamics in pancreatic ОІ-cells and its role in hasic
insulin secretion are not known. Here, we examined the role of actin dynamics
regulated by neuronal Wiskott-Aldrich syndrome protein (N-WASP) and cofilin
in glucose-induced insulin secretion (GIIS). N-WASP, which promotes actin
polymerization through activation of actin nucleation factor Arp2/3 complex,
was activated in insulin-secreting clonal pancreatic ОІ-cells (MIN6-K8
ОІ-cells) by glucose stimulation. Introduction of a dominant-negative mutant
of N-WASP (DN-N-WASP), which lacks G-actin and Arp2/3 complex-binding
region WA, into MIN6-K8 ОІ-cells or knockdown of N-WASP suppressed
GIIS. We performed perifusion experiment using DN-N-WASP-introduced or
N-WASP-knocked down MIN6-K8 ОІ-cells and found that the second phase of
GIIS was specifically reduced. We also found that cofilin, which severs F-actin
in its dephosphorylated (active) form, is converted to the phosphorylated
(inactive) form in MIN6-K8 ОІ-cells by glucose stimulation, thereby promoting
F-actin remodeling. In addition, perifusion experiment using MIN6-K8 ОІ-cells
showed that a dominant-negative mutant of cofilin, which inhibits activation of
endogenous cofilin, or knockdown of cofilin reduced the second phase of GIIS,
indicating that activity of cofilin is critical for the second phase. In contrast, the
first phase of GIIS arises mostly in G-actin-dependent process, in which cofilin
activity predominates over N-WASP activity. Taken together, these results
indicate that actin dynamics, which is regulated by the balance of N-WASP
and cofilin activities, is critical in determining the biphasic response of GIIS.
Islet Biology—Signal Transduction
213-LB
211-LB
Sulfonylureas Act as an Enhancer of Epac2 Activation in cAMPInduced Insulin Secretion
Enabling Structure Base Drug Discovery Using Stabilised Receptors—
Identification of Novel GPR39 Agonists that Stimulate GLP-1 and
Insulin Secretion In Vitro
TOSHIMASA TAKAHASHI, TADAO SHIBASAKI, HARUMI TAKAHASHI, SUGAВ­
WARA KENJI, SUSUMU SEINO, Kobe, Japan
ALASTAIR J.H. BROWN, STEVE ANDREWS, SUE BROWN, MILES CONGREVE, ALI
JAZAYERI, JAYESH PATEL, OLIVER J. MACE, RUDI PRIHANDOKO, BEN TEHAN,
FIONA MARSHALL, Welwyn Garden City, United Kingdom
cAMP is a key signal in ОІ-cells that amplifies insulin secretion. Incretins
such as glucagon-like peptide 1 (GLP-1) stimulate insulin secretion through
cAMP signaling in ОІ-cells. We have shown that Epac2, which belongs to a
new class of cAMP-binding proteins, plays a critical role in incretin-induced
insulin secretion. In addition, we have found that Epac2 is also a target of
sulfonylureas (SUs). Here we have identified and characterized SU binding site
in Epac2. We first predicted the amino acid residues of Epac2 that interact
with SUs by molecular docking simulation, and the predicted amino acids
were mutated individually to alanine in vitro. Analyses of these mutants by
FRET (fluorescence resonance energy transfer), SU binding, and Rap1 activity
revealed that SU-binding site is located in the first cAMP-binding domain A
(cNBD-A) and that binding of SUs to Epac2 depends on SU structures as well
as the state of cAMP binding to Epac2. We also found that SU and cAMP
synergistically activate Epac2 and Rap1. Modeling of cAMP binding and SU
binding in cNBD-A indicates that the two binding sites are not identical, but
clearly overlap, suggesting that cAMP and SU cannot bind simultaneously
in cNBD-A. We next examined the effect of combination of SU and incretin
or cAMP analog on insulin secretion from perfused pancreas. Potentiation
by cAMP analog or GLP-1 of glibenclamide-induced insulin secretion was
markedly enhanced in wild-type mice, whereas the potentiation was
significantly reduced in Epac2 deficient mice. Our data indicate that cAMP
and SU cooperatively activate Epac2 through binding to cNBD-B and cNBD-A,
respectively, to stimulate insulin secretion. We propose that SUs act as an
enhancer of activation of Epac2 by cAMP.
Heptares creates new medicines targeting clinically important GPCRs
(G protein-coupled receptors) through application of a powerful structurebased drug discovery (SBDD) capability. By using stabilised receptors (StaRВ®)
Heptares apply advanced computational and structural analyses together with
fragment-based drug discovery to drive the identification of novel hits and
leads for relevant GPCR targets.
The G-protein-coupled receptor 39 (GPR39) has recently been implicated in
metabolic regulation and pancreatic islet function. In vitro GPR39 responds to
Zn2+ coupling via GО±s and GО±q signalling cascades to increase cAMP and IP1/
Ca2+ respectively. Using our approach we have identified novel GPR39 agonists
that have been used to examine the potential of GPR39 activation for the
treatment of metabolic diseases.
Zn2+ and the identified GPR39 agonists G#01 and G#89 stimulated the
accumulation of cAMP and IP1 in GPR39 transiently transfected HEK293 cells
with EC50(cAMP) 0.84ВµM/4.4ВµM/2.4ВµM and EC50(IP1) 0.6ВµM/14.7ВµM/32.6ВµM
(Zn2+/G#01/G#89). The secretion of insulin and GLP-1 in response to
GPR39 agonism was assessed using the pancreatic ОІ- cell line, NIT-1, and
primary mouse intestinal epithelial cells (mIECs). Zn2+ and G#01/G#89 dosedependently stimulated glucose-dependent insulin secretion from NIT-1 cells
(EC50 0.26ВµM/0.94ВµM/0.45ВµM). Furthermore these effects were significantly
diminished using GPR39 siRNA supporting a specific GPR39-mediated
response. Consistent with their insulin secretory activity Zn2+ and compounds
G#01/G#89 also stimulated GLP-1 secretion from primary mIECs with EC50
values of 1.6ВµM, 1.2ВµM and 3.4ВµM respectively.
In conclusion, GPR39 agonists stimulate insulin and GLP-1 secretion in
vitro from native/primary cell systems and suggest that GPR39 agonists may
represent efficacious agents for the treatment of metabolic disease.
214-LB
Deletion of 4E-BP2 Induces Beta Cell Proliferation and Mass and
Confers Resistance to Streptozotocin Induced Diabetes
MANUEL BLANDINO-ROSANO, JOSHUA SCHEYS, MARGARITA JIMENEZPALOMARES, REBECCA BARBARESSO, NAHUM SONENBERG, ERNESTO
BERNAL-MIZRACHI, Ann Arbor, MI, Montreal, QC, Canada
212-LB
The mechanistic target of rapamycin (mTOR) signaling pathway integrates
growth factors and nutrient signals and is essential for cell growth and
proliferation. The mTOR complex 1(mTORC1) is sensitive to rapamycin and
regulates protein translation and ribosomal biogenesis by modulation of
ribosomal S6 kinase (S6K) and eukaryote initiation factor 4E binding proteins
(4E-BP1 and 2). 4E-BPs repress translation by disrupting eIF4F formation,
thereby preventing ribosome recruitment to the mRNA. To test the role of
4E-BPs in beta cells, we studied 4E-BP1 and 4E-BP2 deficient mice (4ebp1-/and 4ebp2-/-). Mice deficient for 4E-BP1 or 4E-BP2 showed improved glucose
tolerance test at 2 months and 1 year. However, analysis of pancreas
For author disclosure information, see page LB66.
GLP-1 Is Not Able to Preserve the Beta Cell Function in Mice With
Mitochondrial Diabetes
KYONG-HYE JOUNG, YOUNG KYUNG KIM, MIN HEE LEE, MIN JEONG CHOI,
HYUN JUNG HONG, SEUL GI KANG, HYO KYUN CHUNG CHUNG, KOON SOON
KIM, HYUN JIN KIM KIM, KU BON JEONG, MINHO SHONG, Daejeon, Republic
of Korea
Mitochondrial diabetes is an unremarkable form of diabetes characterized
with progressive loss of beta cell function by the mutation of mitochondrial
DNA. Beta cell failure in mitochondrial diabetes is related with imbalance
ADA-Funded Research
LB54
Islet Biology/Insulin Secretion
morphology from these mice showed that beta cell mass and proliferation
was enhanced only in 4ebp2-/- mice. The increase in proliferation in 4ebp2/- mice was associated with higher levels of p-ERK and decrease p27 levels.
Moreover, islets from 4ebp2 -/- mice were resistant to apoptosis induced by
“in vitro” treatment with of pro-inflammatory cytokines (IL1 beta, TNF alpha
and interferon gamma). Finally, 4ebp2-/- mice were resistant to diabetes
induced by low-dose streptozotocin and this protective effect resulted from
lower levels of apoptosis and enhanced proliferation. These experiments
demonstrate that the 4E-BPs relates proliferative and survival signals induced
by activation of mTORC1.
itself to study the molecular pathogenesis of diabetes and as a platform for
aggregating stem cells.
Supported by: NSF (to T.H.H.); NIH (to K.S.A. and R.K.P.B.); HHMI (to K.S.A.)
217-LB
Post-Transcriptional Regulation of SERCA2b by IRS2 in the Pancreatic
Beta Cell
XIN TONG, TATSUYOSHI M. KONO, BEN HALL, DAMIEN DEMOZAY, CHRISTOPHER
J. RHODES, CARMELLA EVANS-MOLINA, Indianapolis, IN, Chicago, IL
Cytosolic and endoplasmic reticulum (ER) Ca2+ levels in the ОІ cell are
closely regulated by the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA)
pump. We have previously shown markedly diminished ОІ cell SERCA2b mRNA
and protein expression in human and rodent models of Type 2 diabetes mellitus
(T2D). To study further the transcriptional and translational regulation of ОІ
cell SERCA2b, we first sought to define the protein and mRNA half-life (t1/2)
under basal and diabetic conditions. SERCA2b protein and mRNA expression
were decreased in INS-1 832/13 cells treated with 5ng/ml IL-1ОІ+25 mM
glucose (IL-1ОІ+HG) to mimic the pro-inflammatory and hyperglycemic milieu
of T2D. Cycloheximide was used to block protein translation and actinomycin
D was used to block transcription in time-course experiments. At baseline,
SERCA2b protein t/12 was ~24hr, while the mRNA t1/2 was ~6hr. IL-1ОІ+HG
reduced the protein t/12 to 16hr, but the mRNA t/12 was stable. IL-1ОІ+HG
led to induction of iNOS and cleaved caspase-3 and reduced SERCA2b protein
t1/2 and expression. However, concurrent treatment with the iNOS inhibitor
L-NMMA prevented these changes, suggesting that SERCA2b loss was NOdependent. Given that iNOS can inhibit IRS/PI3-kinase/Akt signaling, we
further investigated the relationship between this pathway and SERCA2b
expression and stability. INS-1 cells were treated with IGF-1 or infected with
adenoviruses to overexpress IRS-2 or IRS-1. Under basal conditions, IGF1 stimulation and IRS-2, but not IRS-1, increased SERCA2b protein levels.
Interestingly, in IL-1ОІ+HG-treated INS-1 cells, IGF-1 and IRS-2 overexpression
prolonged the protein t1/2 and restored SERCA2b levels. Together, our data
suggest ОІ cell SERCA2b protein t1/2 is decreased in an NO-dependent manner
in T2D. We further demonstrate a novel connection between IRS-2 signaling
and regulation of ER Ca2+, demonstrating that IRS-2 activation regulates
SERCA2b expression under basal conditions and acts to stabilize the protein
under diabetic conditions.
Supported by: NIH
215-LB
Dynamic Changes in Oct4 Expression in Parallel With Human Islet
Dedifferentiation/Redifferentiation In Vitro
ALI ALDIBBIAT, MICHAEL GEORGE WHITE, HUSAIN ALTURAIFI, HELEN MARВ­
SHALL, JAMES SHAW, Newcastle upon Tyne, United Kingdom
It has recently been proposed that beta cell dedifferentiation with loss of
insulin expression and increased expression of mesenchymal markers may
play an important role in the pathogenesis of type 2 diabetes. Animal data
suggest that this is associated with upregulation of pluripotency genes as a
marker of plasticity and potential for beta cell redifferentiation.
We have characterised expression of end-differentiated islet phenotypic
markers, mesenchymal markers and the classical pluripotency marker Oct4 in
intact islets, islet survivor cells (ISCs) established in proliferative 2D culture
and reaggregated pseudo-islets (PIs). Dynamic changes in Oct4 expression
have been further studied by live-cell imaging following infection with a
lentiviral OCT4-eGFP reporter construct in comparison to control CMV-eGFP
construct.
Initial adherence induced proliferation originating as 2D outgrowths
from 3D islet clusters. This was accompanied by decreased expression of
epithelial endocrine markers including insulin, PDX1, PC1/3, Glut2, glucagon,
somatostatin and pancreatic polypeptide and increased expression of CK19,
vimentin and PAX4. Redifferentiation of 3D PIs at Passage 4 led to increased
C-peptide storage and secretion. In parallel, increased Oct4 gene expression
during ISC formation, maintenance in proliferative culture and downregulation
on PI formation was demonstrated. Lentiviral Oct4-eGFP infection confirmed
low frequency of Oct-4 expressing cells in intact islets with increased numbers
on establishment in 2D culture. Live cell imaging demonstrated symmetrical cell
division of OCT4 expressing cells with maintained expression in all progeny. PI
formation was associated with decreased number of cells expressing OCT4eGFP in comparison to control.
Upregulation of Oct4 expression has been demonstrated in human islet cells
undergoing dedifferentiation with reversal following redifferentiation in live
cell reporter gene imaging studies in vitro.
Supported by: K08DK080225; R03DK089147; R01DK093954
216-LB
Pancreatic Primary Cell Aggregates Are Functionally Superior to AgeMatched Islets
THOMAS H. HRAHA, KELLY M.T. SHEKIRO, ABIGAIL B. BERNARD, KRISTI S.
ANSETH, RICHARD K.P. BENNINGER, Aurora, CO, Boulder, CO
Barriers to the effectiveness of islet transplantation include the limited
number of donor islets and post-transplant graft viability. Recently, it has been
shown that smaller islets have higher viability, functionality and lead to better
transplant results. Therefore, a method for controlling the size of transplant
islets may lead to better functional outcomes. To accomplish this, primary
pancreatic cells were dissociated and re-aggregated into �pseudo-islets’
using novel hydrogel microwell arrays created through photo-lithography to
physically direct cell re-aggregation and create pseudo-islets of defined size.
After 7 days in culture, pseudo-islets were created with a mean diameter
of 95 В± 4Вµm and compared to age-matched islets with a mean diameter of
195 В± 23Вµm. Pseudo-islet function was assessed using real-time quantitative
fluorescence microscopy. Compared to age-matched control islets, pseudoislets showed significantly more coordinated [Ca2+]i dynamics at high glucose
and lower [Ca2+]i activity at low glucose. This correlated with elevated
glucose-stimulated insulin secretion. Two-photon microscopy showed a
significant glucose-stimulated NAD(P)H elevation in the pseudo-islets, but not
in the age-matched control islets. In both of these measurements, the pseudoislet response was similar to that of freshly isolated islets.
These data suggest that re-aggregation produces functional islet-like
clusters based on highly-sensitive measurement techniques. Therefore, by
increasing the functional capacity of every donor ОІ-cell, re-aggregating large
islets into smaller pseudo-islets will allow for the therapeutic delivery of
ОІ-cells with greater viability and function. In addition, this method also lends
For author disclosure information, see page LB66.
ADA-Funded Research
LB55
SUBJECT Index
13C-Glucose breath test 87-LB
A1C 27-LB
ABHD6 176-LB
Acarbose 77-LB
ACE C1237T 97-LB
Actin dynamics 210-LB
Acute coronary syndrome 41-LB
Acute hyperglycemia 20-LB
Adhesion molecule 178-LB
Adipocyte biology 137-LB
Adipocyte 178-LB
Adipogenesis 198-LB
Adipose tissue 179-LB, 182-LB, 195-LB
Adolescent 192-LB
Adrenergic denervation 179-LB
Advanced glycation endproducts 157-LB
Adverse cardiovascular events 41-LB
African American 122-LB
Aging 100-LB
Ago-allosteric modulator 67-LB
Akt 137-LB
Albiglutide 52-LB, 54-LB, 55-LB, 57-LB, 58-LB
Alcohol 108-LB
Alogliptin 66-LB
Alpha-MSH 186-LB
AMPK activator 19-LB
Amyloid beta and cellular metabolism 138-LB
Anemia 79-LB
Angiotensin II 141-LB
Animal models 38-LB
Antigen presenting cells 134-LB
Antioxidant status 96-LB
Antioxidant supplements 107-LB
Apolipoprotein C-III 51-LB
Arginine 143-LB, 145-LB
ARNT/HIF1-Гџ 209-LB
Artificial pancreas 37-LB, 49-LB
Aryl hydrocarbon receptor 181-LB
ASBT 171-LB
Asian 26-LB
Assay 94-LB
Atherosclerosis 4-LB
Autoantibodies 94-LB
Autoimmune diseases 132-LB
Bariatric procedure 180-LB
Bariatric surgery 35-LB, 168-LB
Bariatric 192-LB
Basal Plus 47-LB
Beloranib 188-LB
Beta cell dysfunction 212-LB
Beta cell 202-LB, 214-LB, 215-LB, 217-LB
Beta-cell destruction 132-LB
Beta-cell proliferation 205-LB
Biased signaling 191-LB
Bioengineering 216-LB
Biomarker 6-LB, 15-LB, 16-LB
Biphasic insulin secretion 210-LB
Blood glucose monitor 39-LB
Blood pressure 5-LB, 8-LB
Blood retinal barrier 17-LB
Bone 110-LB
Breath test 36-LB
CA Exendin-4 53-LB
Calcium dynamics 216-LB
Camp 213-LB
Canagliflozin 65-LB, 73-LB, 76-LB
Carbohydrate knowledge 26-LB
Carbohydrate restriction 25-LB
Cardio-metabolic 90-LB
Cardiovascular disease 4-LB, 155-LB
Cardiovascular risk factors 69-LB
Carrageenan 158-LB
Cell therapy 203-LB
CGM 91-LB
Children of diabetic mothers 89-LB
Children 90-LB
Cholesterol 79-LB
Cigarette smoking 121-LB
Circadian rhythm 209-LB
Circadian 149-LB, 151-LB
CISH/SOCS2 205-LB
Class III obesity 148-LB
Clinical outcomes 86-LB
Closed-loop 37-LB, 49-LB
CNS 167-LB
CNX_013_B2 18-LB
Coenzyme Q10 195-LB
Cohort 109-LB
Combination therapy 112-LB
Community 113-LB
Comparative effectiveness 85-LB
Computer-guided intravenous insulin system
50-LB
Continuous glucose monitor system 35-LB, 39-LB,
41-LB, 42-LB
Control 37-LB
Coronary artery disease 6-LB, 116-LB
Cost-effectiveness 81-LB
Costs 83-LB
Counterregulation enhancement 1-LB
C-peptide 93-LB
CSII 45-LB
C-Ski 7-LB
Dapagliflozin 62-LB, 70-LB
Dbp 209-LB
Dedifferentiation 215-LB
Depression 30-LB, 33-LB, 197-LB
Developing countries 104-LB
Developing diabetes 61-LB
Development 204-LB
Diabetes and insulin resistance 155-LB
Diabetes education 34-LB
Diabetes management 84-LB
Diabetes mellitus 5-LB, 6-LB, 77-LB
Diabetes risk score 102-LB
Diabetic foot amputation 23-LB
Diabetic foot infection 82-LB
Diabetic foot ulcer 23-LB
Diabetic gastroparesis 10-LB
Diabetic ketoacidosis 92-LB
Diabetic kidney disease 80-LB
Diabetic nephropathy 79-LB
Diabetic neuropathy 11-LB, 104-LB
Diabetic retinopathy 11-LB, 15-LB
Diagnostic techniques and procedures 132-LB
Diet induced obesity 154-LB, 182-LB
Diet 10-LB, 25-LB
DM retinopathy 13-LB
Dorsal vagal complex 152-LB
DPP-4 inhibitor 2-LB, 66-LB, 112-LB
Duodenojejunal bypass 156-LB
Durability 62-LB, 65-LB, 66-LB
DVT 14-LB
Economic 84-LB
LB56
Ectonucleotidases 136-LB
Educational levels 113-LB
Elderly 2-LB, 76-LB
Electronic medical record 106-LB
ELISA 146-LB
Empagliflozin 69-LB, 71-LB, 74-LB
Endocannabinoid 147-LB
Endogenous FAAH inhibitor 147-LB
Endogenous glucose production 71-LB
Endothelial dysfunction 96-LB
Endothelial function 20-LB
Epac2 213-LB
Eqtl 117-LB
ER stress 161-LB
Estrogen receptor 80-LB
Ethnic incidence 148-LB
Exendin-4 60-LB
Exposure to chemicals 193-LB
EZH2 12-LB
Fasiglifam (TAK-875) 67-LB
Fast dissociation 53-LB
Fast-food 109-LB
Fat preference 156-LB
Fetuin-A 108-LB
FFAR1/GPR40 67-LB
FGF19 167-LB
FGF21 159-LB, 161-LB
FNDC5 164-LB
Food intake 152-LB
Fracture 110-LB
Fructose 159-LB
Function 214-LB
G protein-coupled receptor 211-LB
GABA secretion 207-LB
Gastric cancer 128-LB
Gastric electrical stimulation 21-LB
Gastric emptying 180-LB
Gastrointestinal symptoms 10-LB
Gender 115-LB
Gene expression 133-LB
Gene mine 123-LB
Gene-environment interaction 121-LB
Genetic obesity 189-LB, 191-LB
Genetic susceptibility 123-LB
Genetics 118-LB, 122-LB
Genital infections 74-LB
Genome wide association scan 116-LB
Genome-wide association studies 119-LB
Gestational diabetes 97-LB, 98-LB, 109-LB
Glargine 46-LB
Glimepiride 68-LB
Glipizide 62-LB
GLP-1 analogues 206-LB
Glp-1 receptor 170-LB
Glp-1 60-LB, 170-LB, 212-LB
GLP-1R agonist 59-LB
Glucagon inhibition 1-LB
Glucagon receptor antagonist 64-LB
Glucagon 77-LB, 145-LB
Glucagon-like peptide 1 receptor agonist 52-LB,
54-LB, 55-LB, 57-LB, 58-LB
Glucokinase 194-LB
Glucolipotoxicity 202-LB
Gluconeogenesis 149-LB
Glucose control 59-LB, 113-LB
Glucose metabolism 138-LB, 140-LB
Glucose sensors 38-LB
Glucose tolerance 98-LB, 143-LB
Glucose variability 42-LB
GLUT9 72-LB
Glycemic control 21-LB, 46-LB, 63-LB, 70-LB,
86-LB
Glycine 152-LB
Growth factor 15-LB
Growth 95-LB
Hba1c outcomes 85-LB
Health behaviours 9-LB
Heat shock protien 70 23-LB
Hematopoietic cell transplantation 131-LB
Hemoglobin a1c 14-LB
Hepatic fat 150-LB
Hepatic insulin sensitivity 150-LB
Hepatocyte 139-LB
Heritability 117-LB
High fat Diet 155-LB
Hospital quality improvement 50-LB
Hospitalization 106-LB
Human beta cell generation 206-LB
Human duct cell replication 206-LB
Human islets 207-LB
Hydrogels 216-LB
Hyperglycemia 131-LB
Hyperlipidemia 207-LB
Hypertriglyceridemia 51-LB
Hypoglycemia protection 1-LB
Hypoglycemia symptoms 3-LB
Hypoglycemia 2-LB, 28-LB, 68-LB
Hypothalamic inflammation 154-LB
Hypothalamus 153-LB
IADPSG 98-LB
IGF-I 172-LB
IL-8 158-LB
Imeglimin 63-LB
Immunoassay 93-LB
Immunomodulation 56-LB
Impaired awareness of hypoglycemia 3-LB, 28-LB
Impaired glucose tolerance 61-LB
Implantable glucose monitor 39-LB
In vitro 139-LB
Incidence 103-LB
Incretin based therapies 52-LB, 54-LB, 55-LB,
57-LB, 58-LB
Incretin 111-LB, 169-LB, 173-LB
Induced pluripotent stem cells 203-LB
Infections 131-LB
Inflammation 100-LB, 124-LB, 153-LB, 158-LB,
166-LB, 175-LB, 183-LB
Inpatient care 83-LB
Inpatient 84-LB
Insulin dosing knowledge 26-LB
Insulin glargine 43-LB, 47-LB
Insulin glulisine (Apidra) 47-LB
Insulin lispro 46-LB
Insulin resistance 36-LB, 127-LB, 129-LB, 140-LB,
160-LB, 165-LB, 176-LB, 177-LB
Insulin screening 146-LB
Insulin secretion 143-LB, 144-LB, 145-LB, 172-LB,
208-LB
Insulin sensitive obesity 193-LB
Insulin sensitivity 51-LB, 151-LB, 166-LB, 172-LB
Insulin 139-LB, 141-LB, 194-LB
Integrated physiology 157-LB
Interferon 126-LB
Intermittent fasting 11-LB
Internet-delivered lifestyle intervention 81-LB
Intestinal epithelial cells 211-LB
Intestinal microbiota 177-LB
Intravenous glucose tolerance 144-LB
Intravital imaging 160-LB
Irisin 78-LB
Iron 149-LB
IRS2 217-LB
Islet auto-antibodies 40-LB
Islet regeneration 203-LB
Islet stress 136-LB
Islet ОІ-cells 105-LB
Islet 201-LB
IVGTT 192-LB
Ketogenic 25-LB
Ketosis-prone diabetes 40-LB
Lactic acidosis 75-LB
LADA 126-LB
L-cell 75-LB
LDL 29-LB
Leptin 128-LB, 179-LB
Lifestyle intervention 88-LB, 197-LB
Linagliptin 68-LB
Lipid levels 119-LB
Lipolysis products 174-LB
Lipolysis 137-LB, 185-LB
Liraglutide 45-LB, 196-LB
Low glucose suspend 48-LB
Lymphocyte trafficking 124-LB
Macrophage 127-LB, 183-LB
Markov model 81-LB
MCP-1 170-LB
Meal tolerance 144-LB
Medicaid 82-LB
Medical record documentation 99-LB
Medication 110-LB
Melanocortin-4 receptor 189-LB, 191-LB
Memory function in young children 92-LB
Meso scale discovery 93-LB
Metabolic syndrome 87-LB, 159-LB, 178-LB
Metabolites 90-LB
Metap2 Inhibitor 188-LB
Metformin 114-LB, 75-LB
Methionine restriction 182-LB
Mexican American 117-LB
Microfluidics 174-LB
Microglia 153-LB
MIF 134-LB
Mir-200b 12-LB
Mitochondrial diabetes 212-LB
Mitochondrial dynamics 160-LB
Monounsaturated fatty acids (mufas) 147-LB
Mortality 112-LB
Mouse 123-LB
Mtor 141-LB, 204-LB
Mtorc1 214-LB
Muscle 164-LB
Myokine 161-LB
NAFLD 148-LB
NASH 148-LB
New formulation 43-LB
NHANES 102-LB
Nicotinamide 202-LB
Nitric oxide 5-LB
Nocturnal hypoglycemia 48-LB
NOD mouse 56-LB
Non insulin therapies 24-LB
Non-hyperglycemic mice 157-LB
Non-insulin injectable 56-LB
Novel pathway 124-LB
Nrf2 17-LB, 200-LB
Nuclear co-repressor 127-LB
Nuclear magnetic resonance (NMR) spectroscopy
20-LB
Obesity pharmacotherapy 188-LB
LB57
Obesity 175-LB, 176-LB, 181-LB, 183-LB, 190-LB,
194-LB, 196-LB, 197-LB, 32-LB
Obstructive sleep apnea 169-LB
Oct4 215-LB
Online support 31-LB
Outcomes 27-LB
Outpatient care 83-LB
Oxidative stress 154-LB, 195-LB
Pain symptoms 30-LB
Pain 101-LB
Palmitate 201-LB
Pancreatic cancer 111-LB
Pancreatic regenerating protein (reg) 105-LB
Partner/spouse 34-LB
Pediatric diabetes risk reduction 88-LB
Pediatrics 91-LB, 95-LB
Performance 91-LB
Peripheral neuropathy 9-LB
PGC1 alpha 164-LB
Pharmacokinetics 60-LB
Pharmacological chaperone 189-LB
Phase 3 43-LB
Phosphoenolpyruvate 208-LB
Physical activity 42-LB
Plasma triglycerides 21-LB
Pleiotropy 119-LB
Podiatric services 82-LB
Poor rural postpartum women 32-LB
Population genetics 120-LB
PPAR-Оі 7-LB
Pramlintide 49-LB
Prediabetes 33-LB, 150-LB
Pregnancy outcomes 99-LB
Pregnancy 96-LB, 205-LB
Probiotics 177-LB
Programming 204-LB
Prolylcarboxypeptidase 186-LB
Prospect theory 29-LB
Prostate cancer 114-LB
Protein complementation assay 200-LB
Proteomic and metabolomic study 168-LB
Psycho-social needs 34-LB
Pterostilbene 200-LB
Pulmonary embolism 14-LB
Pulse pressure 8-LB
Purinergic receptors 136-LB
Purinergic 120-LB
Pyruvate kinase 208-LB
Quality of life 9-LB
Questionnaire 28-LB
Readmission 106-LB
Refeeding 151-LB
Renal disease 186-LB
Renal outcomes 8-LB
Resveratrol 78-LB
Retinal pigment epithelium 17-LB
Retinopathy 16-LB
Rodent insulin 146-LB
Rxra 18-LB
Safety 24-LB
Screening 87-LB, 104-LB
Self-report 99-LB
Self-tolerance 133-LB
SERCA2b 217-LB
Sevelamer carbonate 80-LB
SGLT1 171-LB
SGLT2 inhibitor 71-LB, 72-LB
Signal transduction 181-LB
SIRT1 162-LB
Sitagliptin 63-LB
Skeletal muscle 162-LB, 165-LB, 190-LB
Sleeve gastrectomy 156-LB
Social media 31-LB
SOCS3 128-LB
Sodium glucose co-transporter 2 (SGLT2) 65-LB,
73-LB, 76-LB
South Asian 173-LB
Staff education 24-LB
Stage 3 chronic kidney disease 73-LB
Statins 61-LB
Stem cell transfusion 133-LB
STEMI 101-LB
Stress 33-LB
Structure-based drug discovery 211-LB
Sulfonylurea 213-LB
Superagonist to GLP-1R 53-LB
Surgical intensive care 50-LB
T2DM 105-LB
TCF7L2 118-LB
Telemetry 38-LB
Testosterone 166-LB
TGF-ОІ1 7-LB
Th22 cells 129-LB
Thermogenesis 185-LB
Threshold suspend 48-LB
Thromboembolism 14-LB
Transcriptome 201-LB
Transtheoretical model 29-LB
TRB3 165-LB
Type 1 diabetes 64-LB, 70-LB, 95-LB, 126-LB, 134LB, 196-LB
Type 2 diabetes 4-LB, 13-LB, 35-LB, 59-LB, 86-LB,
101-LB, 103-LB, 107-LB, 108-LB, 114-LB, 116LB, 118-LB, 121-LB, 122-LB, 129-LB, 168-LB
Ubiquitin ligase 175-LB
UCP1 185-LB
Ultra-rapid insulin 44-LB
LB58
Uric acid 72-LB
Urinary tract infections 74-LB
Validity reliability 36-LB
Vascularization 100-LB
VDR 198-LB
VEGF 12-LB
Veteran 115-LB
Visceral adiposity 13-LB
Vitamin D 30-LB, 198-LB
Vitamins C and E 107-LB
Weight loss 27-LB, 180-LB
Well-being 32-LB
White blood cell type 103-LB
White matter 92-LB
Wnt/LRP6-TCF4 signaling pathway 140-LB
ABSTRACT Author Index
The number following the name refers to the abstract number, not the page number. A number in bold beside an author’s name indicates the
presenting author.
Abbas, Zulfiqarali G. 104‑LB
Abbasakoor, Noormuhammad 84‑LB
Abdelmoneim, Sahar S. 20‑LB
Abdulkarim, Baroj 201‑LB
Ables, Gene P. 182‑LB
Abraham, Varghese 169‑LB
Abuaysheh, Sanaa 166‑LB
Abumrad, Naji N. 148‑LB
Agarwal, Nutan 97‑LB
Aggarwal, Parul 97‑LB
Ahima, Rexford S. 151‑LB
Ahluwalia, Rupa 173‑LB
Ahmann, Andrew 48‑LB
Ahrén, Bo 52‑LB
Akanuma, Yasuo 61‑LB
Aldibbiat, Ali 215‑LB
Alejandro, Emilyn 204‑LB
Alejandro, Rodolfo 136‑LB
Alexander, Veronica J. 51‑LB
Alexandropoulos, Nikolaos 196‑LB
Almaca, Joana 100‑LB, 207‑LB
Alturaifi, Husain 215‑LB
Alves, Tiago 208‑LB
Amatya, Christina 56‑LB
An, Ping 122‑LB
Andel, Michal 132‑LB
Anderson, Robert J. 8‑LB
Andrews, Jeanette S. 122‑LB
Andrews, Steve 211‑LB
Andrews, Susan M. 60‑LB
Andrikopoulos, Sof 123‑LB
Anilkumar, D. 18‑LB
Anseth, Kristi S. 216‑LB
Antoun, Joseph 148‑LB
Anup, O. 18‑LB
Appelhans, Brad 197‑LB
Arakawa, Hiroshi 72‑LB
Archibald, Lennox K. 104‑LB
Arias, Pablo 65‑LB
Armando, Aaron 127‑LB
Armstrong, David 82‑LB
Arnold, Myrtha 156‑LB
Arya, Rector 90‑LB
Asare, Isaac B. 155‑LB
ASPIRE In-Home Study Group 48‑LB
Åsvold, Bjørn Olav 3‑LB
Attvall, Stig 10‑LB
Aubert, Gregory 184‑LB
Augie, Ines 182‑LB
Auwerx, Johan 127‑LB
Awan, Fazli R. 184‑LB
Ayala, Julio E. 170‑LB
Aye, Tandy 92‑LB
Babor, Richard 35‑LB
Bagarolli, Renata A. 177‑LB
Bahn, Gideon 8‑LB
Bailey, Clifford J. 63‑LB
Bailey, Kathleen A. 118‑LB
Bailey, Timothy S. 91‑LB
Bakris, George 73‑LB
Baldi, Simona 71‑LB
Balis, Dainius A. 65‑LB
Bandyopadhyay, Gautam 127‑LB
Bansal, Vivek 84‑LB
Barbaresso, Rebecca 214‑LB
Barbier, Maryse 19‑LB
Barendse, Shalleen 28‑LB
Barnea-Goraly, Naama 92‑LB
Baron, Alain 75‑LB
Barone, Francesca 124‑LB
Bass, Joseph T. 151‑LB
Basterra-Gortari, Francisco Javier 109‑LB
Basu, Ananda 20‑LB, 150‑LB
Basu, Rita 150‑LB
Batra, Manav 166‑LB
Bauer, Tim 16‑LB
Bayona, Zarana 95‑LB
Bayrak, Elif Seyma 42‑LB
Beban, Grant 35‑LB
Beck, Roy 92‑LB
Becker, Dorothy J. 99‑LB
Beekman, Marian 119‑LB
Bell, Graeme I. 118‑LB
Below, Jennifer 117‑LB
Benasi, Kari 37‑LB
Benninger, Richard K. 216‑LB
Benoit, Stephen 192‑LB
Bequette, B. Wayne 37‑LB
Bergenstal, Richard M. 48‑LB
Berggren, Per-Olof 100‑LB, 207‑LB
Bergman, Richard N. 144‑LB, 155‑LB, 167‑LB,
194‑LB
Bernal-Lopez, Rosa 198‑LB
Bernal-Mizrachi, Ernesto 204‑LB, 214‑LB
Bernard, Abigail B. 216‑LB
Beserab, Anatole 79‑LB
Bes-Rastrollo, Maira 109‑LB
Beta Cell Team of FNIH Biomarkers Consortium
143‑LB, 144‑LB, 145‑LB
Bhanot, Sanjay 51‑LB
Bhargava, Tina 81‑LB
Bhattacharyya, Sumit 158‑LB
Bhatwadekar, Ashay D. 11‑LB
Bielak, Lawrence F. 122‑LB
Birnbaum, Morris J. 137‑LB
Bishop, Michael 171‑LB
Bizet, Florence 43‑LB
Bjørgaas, Marit R. 3‑LB
Blackman, Brett 139‑LB
Blandino-Rosano, Manuel 214‑LB
Blangero, John 90‑LB
Blankfard, Martin 146‑LB
Bluck, Les 172‑LB
Bode, Bruce W. 48‑LB, 57‑LB, 76‑LB
Bogle, Allyson 70‑LB
Bolli, Geremia B. 43‑LB
Booth, Michael 35‑LB
Bottu, Guy 201‑LB
Bottum, Kathleen 181‑LB
Bouchard, Jonathan R. 85‑LB
Boucher, Jackie L. 27‑LB
Boulton, Michael E. 11‑LB
Bracy, Deanna P. 167‑LB
Brockway, Robert 38‑LB
Broedl, Uli C. 69‑LB, 71‑LB, 74‑LB
Broussard, Josiane L. 155‑LB
Brown, Alastair J. 211‑LB
Brown, Sue 211‑LB
Bryce, Cindy L. 81‑LB
Buckingham, Bruce 37‑LB, 91‑LB, 92‑LB
LB59
Buckley, Christopher D. 124‑LB
Buenaventura, Jefi Jaustine 99‑LB
Buring, Julie E. 107‑LB
Burkey, Jennifer 51‑LB
Burn, Paul 56‑LB
Busch, Andrew M. 197‑LB
Buse, John 111‑LB, 75‑LB
Busik, Julia V. 11‑LB
Busta, Agustin 80‑LB
Byrn, Mary 30‑LB
Cade, Brian 122‑LB
Cai, Weijing 80‑LB, 157‑LB
Caicedo, Alejandro 100‑LB, 207‑LB
Caldwell, Jody 156‑LB
Cameron, Fraser 37‑LB
Camisasca, Riccardo 66‑LB
Camp, Anne 88‑LB
Candelaria, Karla 184‑LB
Canney, Lori 44‑LB
Canovatchel, William 65‑LB
Capalbo, Donatella 172‑LB
Caprio, Sonia 88‑LB
CARDIoGRAMplusC4D 116‑LB
Cardona, Fernando 198‑LB
Carpentier, André 195‑LB
Carr, Molly C. 54‑LB, 58‑LB
Carria, Lori R. 49‑LB
Carter, Lauren 175‑LB
Carvalho, Ana 6‑LB
Carvalho, Bruno M. 177‑LB
Casella-Filho, Antonio 6‑LB
Casteilla, Louis 195‑LB
Castellano-Castillo, Daniel 198‑LB
Catalano, Patrick 98‑LB
Cato, Allison 92‑LB
Cefalu, William T. 65‑LB
Cengiz, Eda 49‑LB
Cerna, Marie 132‑LB
Cha, Eunme 115‑LB
Chakrabarti, Subrata 12‑LB
Chalamandaris, Alexandros-Georgios 70‑LB
Chambers, Adam P. 180‑LB
Chan Lee, Won 85‑LB
Charles, Matt 56‑LB
Charron-Prochownik, Denise 99‑LB
Chase, Geoffery 35‑LB
Chase, Peter 91‑LB
Chaudhry, Zunaira 187‑LB
Chaudhuri, Ajay 166‑LB
Chen, Alice 188‑LB
Chen, Angela 204‑LB
Chen, Chen 17‑LB
Chen, Danny 144‑LB
Chen, Guanje 122‑LB
Chen, Julie 179‑LB
Chen, Li 129‑LB
Chen, Lihong 171‑LB
Chen, Rony 89‑LB
Chen, Wei-Min 122‑LB
Chen, Xinhua 96‑LB
Chen, Xue 80‑LB
Chen, Yingxian 185‑LB
Cheng, Lei 151‑LB
Cheng, Peiyao 92‑LB
Chernoff, Arthur 14‑LB
Chiamvimonvat, Nipavan 4‑LB
Chimen, Myriam 124‑LB
Chino, Yukihiro 72‑LB
Chism, Jack P. 60‑LB
Chittoor, Geetha 90‑LB
Choi, Hyung Jin 110‑LB
Choi, In Young 53‑LB, 59‑LB
Choi, Jessica 99‑LB
Choi, John 29‑LB
Choi, Min Jeong 212‑LB
Choi, Soomin 59‑LB
Chu, Qingwei 137‑LB
Chuang, Eunice Y. 84‑LB
Chun, Kelly Y. 93‑LB
Chung, Hyo Kyun Chung 212‑LB
Chung, Sookja K. 185‑LB
Chung, Stephen S. 185‑LB
Ciardella, Antonio 16‑LB
Cinar, Ali 42‑LB
Cinar, Resat 147‑LB
Cipriani, Yolanda 164‑LB
Cirkel, Deborah 52‑LB, 54‑LB
Cistrone, Monica 99‑LB
Clark, Michelle 78‑LB
Clemente-Postigo, Mercedes 198‑LB
Clements, Mark 39‑LB
Clements, Ronald H. 148‑LB
Clinton, Paula 37‑LB
Close, Kelly 83‑LB
Cmrecˇnjak, Jasna 101‑LB
Cnop, Miriam 201‑LB
Cobelli, Claudio 144‑LB, 150‑LB
Coen, Paul M. 190‑LB
Cohen, Neale 47‑LB
Collins, Andrew W. 5‑LB
Collins, Jon 171‑LB
Comuzzie, Anthony G. 90‑LB
Congreve, Miles 211‑LB
Connor, Tim 138‑LB
Coskun, Tamer 38‑LB
Cowan, David 171‑LB
Cox, Nancy J. 117‑LB
Cox, Rachel M. 25‑LB
Crawford, Sybil 197‑LB
Crooke, Rosanne M. 51‑LB
Cruz, Miguel 117‑LB
Cundy, Tim 35‑LB
Cunnion, Kenji M. 130‑LB
C´uri´c, Korana 101‑LB
Curran, Joanne E. 90‑LB
Currie, Craig J. 112‑LB
Czeczor, Juliane K. 138‑LB
Da Silva, Alexandre A. 186‑LB
Da Silva, Jussara M. 186‑LB
Da Silva, Natalia T. 177‑LB
Dalal, Krishna 97‑LB
D’Alessio, David A. 180‑LB, 192‑LB
Dalla Man, Chiara 144‑LB, 150‑LB
Dandona, Paresh 166‑LB
Daniels, Mark 91‑LB
Das, Nibhriti 97‑LB
Das, Swapan 117‑LB
Dash, Ajit 139‑LB
Daubenmier, Jennifer J. 25‑LB
Davies, Melanie 73‑LB
Davis, Cecilia 179‑LB
Davis, Dianne 78‑LB
De Aguiar, Renata B. 140‑LB
De la Fuente, Carmen 109‑LB
De Souza, Errol 44‑LB
De Zeeuw, Dick 73‑LB
Deering, Tye 139‑LB
DeFronzo, Ralph A. 75‑LB, 90‑LB
Dekoven, Mitchell 85‑LB
Del Prato, Stefano 62‑LB, 66‑LB
Delebecque, Fanny 169‑LB
Demozay, Damien 217‑LB
Dennis, Edward 127‑LB
D’Eramo Melkus, Gail 131‑LB
Derazne, Estella 89‑LB
Desai, Mehul 76‑LB
Deschamps, Ketra 106‑LB
Despa, Florin 4‑LB
Despa, Sanda 4‑LB
Dey, Adwitia 5‑LB
Dhindsa, Sandeep 166‑LB
Dhir, Ravindra 151‑LB
Diamant, Michaela 63‑LB
Diaz, Ana 99‑LB
Ding, Ying 64‑LB
DiPilato, Lisa M. 137‑LB
Dixit, Snehil 9‑LB
Dobbins, Robert L. 171‑LB
Dohi, Taeko 128‑LB
Dolan, Lawrence M. 192‑LB
Dominguez, James 11‑LB
Dominguez, Ligia J. 109‑LB
Dong, Fran 94‑LB
Dong, Hua 4‑LB
Dong, Jessica 83‑LB
Dong, Xinyuan 179‑LB
Dougan, Michael 83‑LB
Doyle, Todd 30‑LB
Draznin, Boris 86‑LB
Dronavalli, Suma 169‑LB
Du, Xueping 113‑LB
Dube, Simmi 150‑LB
Dubis, Gabriel S. 190‑LB
Duckworth, William 8‑LB
Dugan, Colleen E. 174‑LB
Duggirala, Ravindranath 90‑LB
Dugi, Klaus A. 68‑LB
Dunger, David B. 172‑LB
Dupuis, Josée 121‑LB
Durán-Garcia, Santiago 62‑LB
Dushay, Jody 159‑LB
Dziura, James 88‑LB
Eby, Elizabeth 106‑LB
Eckert, Emily A. 148‑LB
Edelman, Steven V. 46‑LB
Edukulla, Ramakrishna 203‑LB
Edwy, Marjan 85‑LB
Eggen, Silje A. 3‑LB
Eguchi, Jun 178‑LB, 183‑LB
Eizirik, Decio L. 201‑LB
El Khatib, Moustafa 135‑LB
Elango, Bhakkiyalakshmi 200‑LB
Elder, Deborah 192‑LB
Ellefson, Jacob 56‑LB
Elliot, Sharon J. 80‑LB
El-Remessy, Azza B. 15‑LB
Emanuele, Mary Ann 30‑LB
Emanuele, Nicholas 8‑LB
Emmett, Matt 137‑LB
ENGAGE Consortium 119‑LB
Errazuriz Cruzat, Isabel 150‑LB
Escobedo, Jorge 117‑LB
Espinosa-Heidmann, Deigo 15‑LB
Ethridge, John K. 98‑LB
Evans, Mark L. 47‑LB
Evans-Molina, Carmella 187‑LB, 217‑LB
Fang, Donghong 45‑LB
LB60
Fang, Yixin 29‑LB
Farfel, Alon 89‑LB
Farhy, Leon S. 1‑LB
Farook, Vidya S. 90‑LB
Farooq, Amina 15‑LB
Favarato, Desiderio 6‑LB
Feferman, Leonid 158‑LB
Fernandez-Garcia, Diego 198‑LB
Ferrannini, Ele 71‑LB
Ferreira, Teresa 119‑LB
Fineman, Mark 75‑LB
Finkelstein, Joseph 115‑LB
Fiorina, Paolo 136‑LB
Fisher, Deirdre 42‑LB
Fisher, Ffolliott M. 159‑LB
Fleck, Penny 66‑LB
Florez, Jose 120‑LB
Floyd, Elizabeth 175‑LB
Flynn, Charles R. 148‑LB
Forga, Lluis 109‑LB
Fotino, Carmen 136‑LB
Fouda, Abdelrahman 15‑LB
Fouqueray, Pascale 63‑LB
Fowler, Sharon P. 90‑LB
Foygel, Kira 200‑LB
Franco, Marietta 79‑LB
Franz, Marion J. 27‑LB
Frascerra, Silvia 71‑LB
Friedberg, Jennifer 29‑LB
Friedman, David 120‑LB
Frier, Brian M. 28‑LB, 3‑LB
Fryburg, David A. 143‑LB, 144‑LB, 145‑LB
Fu, Hanjing 113‑LB
Fu, Wuxia 51‑LB
Fung, Albert 76‑LB
Gaddy, James R. 60‑LB
Galinier, Anne 195‑LB
Gallwitz, Baptist 68‑LB
Gamazon, Eric 117‑LB
Garcia, Anna 148‑LB
Garduno Garcia, Jose de Jesus 164‑LB
Garg, Satish K. 48‑LB
Garhyan, Parag 64‑LB
Garrido-Sanchez, Lourdes 198‑LB
Garrison, Herbert G. 50‑LB
Gassmann-Mayer, Cristiana 73‑LB, 76‑LB
Gauthier, Marie-Soleil 193‑LB
Gaziano, J. Michael 107‑LB
Ge, Junbo 41‑LB
Gea, Alfredo 109‑LB
Geary, Richard 51‑LB
Gelwicks, Steve 106‑LB
Genders, Amanda J. 138‑LB
Geng, Dawei 193‑LB
George, Tom 106‑LB
Gerich, John 69‑LB, 74‑LB
Ghanim, Husam 166‑LB
Ghosh, Sangeeta 164‑LB
Ghosh, Sujoy 175‑LB
Gibbs, Joanna 86‑LB
Glass, Chirstopher 127‑LB
Glass, Leonard C. 46‑LB
Glavaš, Edgar 101‑LB
Glynn, Robert J. 107‑LB
Goel, Anuj 116‑LB
Gokhale, Mugdha 111‑LB
Goldman, Veronica 25‑LB
Gong, Zhenwei 184‑LB
Goodpaster, Bret 190‑LB
Goodyear, Laurie J. 160‑LB, 165‑LB
Gradišer, Marina 101‑LB
Graf, Rolf 105‑LB
Graham, Mark J. 51‑LB
Grant, Maria B. 11‑LB
Grassi, Fabio 136‑LB
Gray, Chris 111‑LB
Green, Kelly 166‑LB
Gregg, Brigid 204‑LB
Grenier-Larouche, Thomas 195‑LB
Griebel, Thasso 201‑LB
Griffen, Steven C. 70‑LB
Grisé, Kenneth N. 5‑LB
Gu, Xiaoning 113‑LB
Guddattu, Vasudevan 9‑LB
Guo, Xiuqing 122‑LB
Gupta, S.K. 23‑LB
Gutierrez-Juarez, Roger 179‑LB
Guyer, Katherine M. 94‑LB
Ha, Yong-Chan 110‑LB
Habata, Yugo 67‑LB
Hach, Thomas 69‑LB, 74‑LB
Haefner, Paul 38‑LB, 39‑LB
Haffner, Steven M. 103‑LB
Hagan, Scott 78‑LB
Hägg, Sara 119‑LB
Hair, Pamela 130‑LB
Hale, Daniel E. 90‑LB
Hall, Ben 217‑LB
Hall, John E. 186‑LB
Hamdy, Osama 84‑LB
Hammer, Marilyn J. 131‑LB
Hammock, Bruce 4‑LB
Han, Jennifer Y. 126‑LB
Hanis, Craig L. 117‑LB
Hanley, Anthony J. 103‑LB
Hansen, Liz-Iren 3‑LB
Hantel, Stefan 69‑LB, 74‑LB
Hara, Manami 118‑LB
Harbord, Nikolas 80‑LB
Hardee, Sandra D. 50‑LB
Hardwick, Christine 106‑LB
Hardy, Thomas A. 64‑LB
Harris, Stewart 76‑LB
Harris, Todd 4‑LB
Hartiala, Jaana 116‑LB
Hatanaka, Masayuki 187‑LB, 209‑LB
Hawkins, Matthew 86‑LB
Hawkins, Meredith 179‑LB
Hecht, Frederick M. 25‑LB
Hehnke, Uwe 2‑LB, 68‑LB
Heise, Tim 71‑LB
Helbling, Nicole L. 190‑LB
Hellmann, Pattie H. 1‑LB
Heneberg, Petr 132‑LB
Henry, Robert R. 2‑LB, 70‑LB
Herman, Mark A. 159‑LB
Herman, William 99‑LB
Hernandez, Javier 114‑LB
Hershey, Tamara 92‑LB
Hess, Rachel 81‑LB
Highland, Heather M. 117‑LB
Hirshman, Michael F. 165‑LB
Hivert, Marie France 122‑LB
Hockey, Andrew 47‑LB
Hod, Moshe 89‑LB
Hodge, Rebecca J. 60‑LB
Holliday-White, Kimberly 39‑LB
Holterman, Mark 133‑LB
Home, Philip D. 43‑LB, 58‑LB
Hompesch, Marcus 59‑LB
Hong, Hyun Jung 212‑LB
Hong, Jaeyoung 122‑LB
Horikoshi, Momoko 119‑LB
Hottenga, Jouke-Jan 119‑LB
Houmard, Joseph A. 190‑LB
Hraha, Thomas H. 216‑LB
Hu, Frank B. 108‑LB
Hu, Gang 102‑LB
Huang, Hui 189‑LB
Huang, Jingyu 149‑LB
Huang, Jun-Yuan 184‑LB
Huang, Wenyu 151‑LB
Hueb, Whady 6‑LB
Hughes, Thomas E. 188‑LB
Hunt, Kelly J. 90‑LB
Hwang, Sang Youn 53‑LB
Iatridis, James C. 157‑LB
Iglesias, José 176‑LB
Igrec, Miljenka 101‑LB
Ikeda, Yasuhiro 135‑LB, 203‑LB
Illien-Junger, Svenja 157‑LB
Inagaki-Ohara, Kyoko 128‑LB
Inge, Tom 192‑LB
Inkster, Berit 28‑LB
Inoue, Hiroshi 161‑LB
Inzucchi, Silvio E. 2‑LB, 63‑LB
Irvin, Marguerite R 122‑LB
Ito, Chikako 61‑LB
Ito, Ryo 67‑LB
Iwamoto, Yasuhiko 61‑LB
Jackson, Charles V. 38‑LB
Jackson, Kaleena 4‑LB
Jaeger, Cassie 181‑LB
Jaffe, Allan 20‑LB
Jagannath, M.R. 18‑LB
James, June R. 24‑LB
Jang, Hyun-Ju 141‑LB
Jang, Sunmee 110‑LB
Jarres, Russell 146‑LB
Jayaraman, Sundararajan 133‑LB
Jazayeri, Ali 211‑LB
Jenkins, Todd 192‑LB
Jenkins-Jones, Sara 112‑LB
Jenkinson, Christopher P. 90‑LB
Jensen, Majken K. 108‑LB
Jensen, Richard A. 122‑LB
Jeong, Ku Bon 212‑LB
Ji, Yu 113‑LB
Jiang, Ling 94‑LB
Jiang, Zhen Y. 184‑LB
Jiao, Yang 205‑LB
Jimenez, Monik C. 108‑LB
Jimenez-Palomares, Margarita 214‑LB
Johnson, Jennal 46‑LB
Johnson, Nicole 31‑LB, 34‑LB
Johnson, Susan 52‑LB
Joly, Erik 176‑LB
Jones-Leone, Angela 55‑LB
Jørgensen, Sine W. 172‑LB
Joung, Kyong-Hye 212‑LB
J-PREDICT Study Investigators 61‑LB
Jullig, Mia 168‑LB
Jung, Dae Young 163‑LB
Jung, Sangmin 29‑LB
Juul, Anders 172‑LB
Kabagambe, Edmond K. 122‑LB
Kadowaki, Takashi 61‑LB
Kaestner, Klaus 205‑LB
Kahn, Richard 83‑LB
Kai, Alan K. 185‑LB
Kalaj, Anita 80‑LB
Kalil, Roberto 6‑LB
Kampino, Gadi 89‑LB
LB61
Kang, Ja Hoon 59‑LB
Kang, Li 158‑LB
Kang, Seul Gi 212‑LB
Kanoni, Stavroula 116‑LB
Kapitza, Christoph 64‑LB
Kasichayanula, Sreeneeranj 70‑LB
Kati´c, Maša 101‑LB
Kato, Seiya 128‑LB
Kaufman, Francine R. 48‑LB
Kaye, Joey 44‑LB
Kazda, Christof M. 64‑LB
Ke, Weijian 45‑LB
Kelly, Ronan P. 64‑LB
Kenji, Sugawara 213‑LB
Kennedy, Amy 124‑LB
Kennedy, Robert 174‑LB
Khan, Abdul R. 184‑LB
Kibbey, Richard G. 208‑LB
Kikuchi, Naoya 67‑LB
Kilimnik, Jerry 118‑LB
Kilroy, Gail 175‑LB
Kim, Dennis D. 188‑LB
Kim, Gabriel 69‑LB, 74‑LB
Kim, Grace 88‑LB
Kim, Hae-Suk 141‑LB
Kim, Hyun Jin Kim 212‑LB
Kim, Jason K. 163‑LB
Kim, Jeong-a 141‑LB
Kim, Jongoh 14‑LB
Kim, Koon Soon 212‑LB
Kim, Sarah 25‑LB
Kim, Se Min 14‑LB
Kim, Terri 75‑LB
Kim, Yong Kyun 13‑LB
Kim, Young Hoon 53‑LB
Kim, Young Kyung 212‑LB
Kirby, Brenda 20‑LB
Kirk-Ballard, Heather 175‑LB
Kishimoto, Junji 61‑LB
Kitazato, Hiroji 61‑LB
Kleber, Marcus 116‑LB
Klonoff, David C. 48‑LB
Knobf, M. Tish 131‑LB
Knop, Filip K. 173‑LB
Ko, Hwi Jin 163‑LB
Kobayashi, Yumiko 151‑LB
Kocalis, Heidi 154‑LB
Koh, Angela 26‑LB
Koh, Eun Kyung 141‑LB
Koh, Ho-Jin N. 165‑LB
Koh, Pei Ling 26‑LB
Kolattukudy, Pappachan E. 170‑LB
Koliwad, Suneil K. 153‑LB
Kolka, Cathryn M. 155‑LB
Kollman, Craig 92‑LB
Komatsu, Hidetoshi 67‑LB
Kondo, Manabu 209‑LB
Kono, Tatsuyoshi M. 187‑LB, 217‑LB
Koren, Shlomit 137‑LB
Krager, Stacey 181‑LB
Krasner, Alan 44‑LB
Krishnarajah, Janakan 44‑LB
Kruckelmann, Friederike 80‑LB
Kucera, Petr 132‑LB
Kudva, Yogish C. 135‑LB, 203‑LB
Kuhadiya, Nitesh 166‑LB
Kulkarni, Bhushan V. 180‑LB
Kumar, Anil 23‑LB
Kumar, Ashok 23‑LB
Kumar, Ashok R. 18‑LB
Kumar, Jitender 116‑LB
Kumusoglu, Doga 204‑LB
Kunos, George 147‑LB
Kuo, Shihchen 81‑LB
Kurahashi, Kiyoe 161‑LB
Kwee, Lydia 116‑LB
Kwon, Se Chang 53‑LB, 59‑LB
Ladenvall, Claes 116‑LB, 119‑LB
Laffel, Lori 91‑LB
Lagakos, William S. 127‑LB
Lagou, Vasiliki 119‑LB
Lam, Karen S. 185‑LB
Lam, Tony K. 152‑LB
Langer, Jakob 85‑LB
Langkilde, Anna Maria 62‑LB
Langslet, Gisle 65‑LB
Laron, Zvi 89‑LB
Laron-Kenet, Tamar 89‑LB
Lauritzen, Hans P. 160‑LB
Le, Bach 4‑LB
Lebovitz, Harold E. 21‑LB, 63‑LB
Lee, Douglas S. 143‑LB, 144‑LB, 145‑LB
Lee, Kyu Hang 53‑LB
Lee, Min Hee 212‑LB
Lee, Min-Young 165‑LB
Lee, Richard G. 51‑LB
Lee, Soo Jin 202‑LB
Lee, Tyson 79‑LB
Lee, Yongjin 163‑LB
Lee, Young-Kyun 110‑LB
Lehman, Donna M. 90‑LB, 114‑LB
Leiter, Lawrence A. 65‑LB
LeLay, John 205‑LB
Lemon, Stephenie C. 197‑LB
Leong, Robert 79‑LB
Lepouras, Antonios 196‑LB
Lertwattanarak, Raweewan 164‑LB
Levandoski, Lucy 92‑LB
Ley, Sylvia H. 108‑LB
Li, Fangyong 88‑LB
Li, Guohua 77‑LB
Li, Hai 45‑LB
Li, Li 33‑LB
Li, Ling 105‑LB
Li, Man 122‑LB
Li, Ning 4‑LB
Li, Pingping 127‑LB
Li, Siming 163‑LB
Li, Weijie 179‑LB
Li, Yanbing 45‑LB
Li, Yinming 41‑LB
Li, Yue 113‑LB
Li, Yuling 113‑LB
Liang, Hanyu 164‑LB
Liao, Lizhen 77‑LB
Liljenquist, David R. 91‑LB
Lin, Iris 29‑LB
Lin, Jiandie 163‑LB
Lin, Jiang 60‑LB
Lin, Yuhong 147‑LB
Linardi, Anastasia 196‑LB
Lipp, Sonia 180‑LB
Lipps, Janie 78‑LB
Littlejohn, Elizabeth 42‑LB
Liu, Bing 179‑LB
Liu, Ching-Ti 121‑LB, 122‑LB
Liu, De min 7‑LB
Liu, Jie 147‑LB
Liu, Jingmin 122‑LB
Liu, Juan 45‑LB
Liu, Liehua 45‑LB
Liu, Rong 46‑LB
Liu, Yaping J. 171‑LB
López Alarcón, Mardia Guadalupe 36‑LB
Lorenzo, Carlos 103‑LB, 114‑LB
Lovell-Badge, Robin 184‑LB
Lu, Min 127‑LB
Lu, Young 157‑LB
Lum, Helen 164‑LB
Lutale, Janet 104‑LB
Lv, Yujie 113‑LB
Lynch, Jane L. 90‑LB
Lynn, Marissa H. 83‑LB
Lysek, Robert 19‑LB
Lyssenko, Valeriya 120‑LB
Ma, Yunsheng 197‑LB
MacDougald, Ormond 174‑LB
Mace, Oliver J. 211‑LB
Macias-Gonzalez, Manuel 198‑LB
Madhusudan, R. 18‑LB
Madiraju, Murthy 176‑LB
Maeda, Risa 67‑LB
Maemura, Koji 61‑LB
Mägi, Reedik 119‑LB
MAGIC Investigators 122‑LB
Mahajan, Anubha 119‑LB
Maiya, Arun G. 9‑LB
Makdissi, Antoine 166‑LB
Makino, Hirofumi 178‑LB, 183‑LB
Maldonado-Hernández, Jorge 36‑LB, 87‑LB
Malekzadeh, Reza 140‑LB
Malone, Kaitlin 99‑LB
Maneva-Radicheva, Lilia 56‑LB
Mangiafico, Salvatore 123‑LB
Mani, Arya 140‑LB
Mani, Sheida 140‑LB
Manojkumar, S. 18‑LB
Manson, JoAnn E. 107‑LB, 108‑LB
Mansuy-Aubert, Virginie 184‑LB
Mantha, Kamala 80‑LB
Maranhao, Raul C. 6‑LB
Maratos-Flier, Eleftheria 159‑LB
Marchetti, Piero 201‑LB
Marcheva, Biliana 151‑LB
Marcovecchio, Loredana 172‑LB
Margulies, Kenneth B. 4‑LB
Mari, Andrea 71‑LB
Marjason, Joanne 188‑LB
Marks, Jennifer 8‑LB
Marks-Shulman, Pamela 148‑LB
Marquis, Alison 111‑LB
Marselli, Lorella 201‑LB
Marshall, Fiona 211‑LB
Marshall, Helen 215‑LB
Martin, Ashley 124‑LB
Martinez Basila, Azucena 36‑LB
Martínez Razo, Gabriel 87‑LB
Martínez-Basila, Azucena 87‑LB
Martinez-Gonzalez, Miguel Angel 109‑LB
Marukian, Svetlana 139‑LB
Marullo, Letizia 119‑LB
Mathur, Ruchi 194‑LB
Matragoon, Suraporn 15‑LB
Matsen, Miles E. 167‑LB
Matsuda-Nagasumi, Kae 67‑LB
Matsuzaki, Goro 128‑LB
Matute González, María Guadalupe 36‑LB
Mauras, Nelly 92‑LB
Mauriello, Clifford 130‑LB
McAllister, Andres 19‑LB
McCall, Anthony L. 1‑LB
McCarthy, Mark I. 119‑LB, 201‑LB
McClain, Donald A. 149‑LB
McDonald, Matthew W. 5‑LB
McGee, Sean 138‑LB
McGettrick, Helen M. 124‑LB
McGrath, Louise 172‑LB
LB62
McKee, Elizabeth 80‑LB
McNulty, Judi 171‑LB
McTigue, Kathleen M. 81‑LB
Meek, Thomas H. 167‑LB
Mehlburger, Ludwig 68‑LB
Mehler, Robert E. 16‑LB
Meier, Juris J. 173‑LB
Meigs, James B. 121‑LB, 122‑LB
Meininger, Gary 65‑LB, 73‑LB, 76‑LB
Meister, Daniel 204‑LB
Melito, Julie 146‑LB
Melling, Jamie W. 5‑LB
Melton, Stephanie 31‑LB, 34‑LB
Mendrick, Edward 20‑LB
Menegaz, Danusa 207‑LB
Meng, Zhuoxian 163‑LB
Meredith, Melissa 48‑LB
Merriam, Philip 197‑LB
Merrins, Matthew 204‑LB
Metacure Study Group 21‑LB
Miao, Dongmei 94‑LB
Michaud, Andréanne 195‑LB
Middleditch, Martin 168‑LB
Mihailov, Evelin 116‑LB
Milicˇi´c, Davor 101‑LB
Miller, Rehae 11‑LB
Millington, Dawn 65‑LB
Mills, Joseph L. 82‑LB
Ming-jing, Bao 40‑LB
Minokoshi, Yasuhiko 128‑LB
Mirmira, Raghavendra G. 187‑LB
Mitchell, Creighton 149‑LB
Mitten, Emilie K. 159‑LB
Miyake, Masato 161‑LB
Miyawaki, Kazumasa 67‑LB
Mo, Xiuu-Lei 191‑LB
Mobley, Sandra 32‑LB
Mohamed, Islam N. 15‑LB
Mohan, Birunda 90‑LB
Mokhlesi, Babak 169‑LB
Molano, R. Damaris 136‑LB
Molina, Judith T. 100‑LB, 207‑LB
Monks, Bob 137‑LB
Montanya, Eduard 206‑LB
Monteleone, Jon 75‑LB
Moolemath, Yoganand 18‑LB
Morahan, Grant 123‑LB
Moran, Patricia 25‑LB
Moreno-Santos, Inmaculada 198‑LB
Morgan, Christopher L. 112‑LB
Mori, Masaaki 67‑LB
Morin, Johane 176‑LB
Morris, Andrew P. 119‑LB, 122‑LB
Morris, David L. 187‑LB
Morton, Anna 24‑LB
Morton, Gregory J. 167‑LB
Moskowitz, Judith T. 25‑LB
Moss, Dan 187‑LB
Muehlen-Bartmer, Isabel 43‑LB
Mugabo, Yves 176‑LB
Mukherjee, Jayanti 112‑LB
Mulvagh, Sharon L. 20‑LB
Mumby, Patricia 30‑LB
Muñoz-Garach, Araceli 198‑LB
Murakami, Kazutoshi 178‑LB
Murphy, Elizabeth 25‑LB
Murphy, Rinki 35‑LB, 168‑LB
Muscelli, Elza 71‑LB
Musi, Nicolas 164‑LB
Muzzin, Patrick 19‑LB
Mysona, Barbara A. 15‑LB
Nacher, Montserrat 206‑LB
Nagao, Yuko 209‑LB
Naik, Sarita 140‑LB
Nakabayashi, Hiroko 209‑LB
Nakamura, Katherine 91‑LB
Nakanishi, Takeo 72‑LB
Nakatsuka, Atsuko 178‑LB
Nalls, Michael A. 122‑LB
Nam, Hong Gil 100‑LB
Narendran, Parth 124‑LB
Nash, Gerard 124‑LB
Natarajan, Sundar 29‑LB
Nauck, Michael 2‑LB, 55‑LB, 62‑LB
Neff, Thomas B. 79‑LB
Negi, Anuradha 26‑LB
Nelson, Chris 116‑LB
Nelson, Michael D. 155‑LB
Ng, Maggie 122‑LB
Nguyen, Dung 11‑LB
Niemeyer, Günter 37‑LB
Niswender, Kevin 154‑LB, 78‑LB
Niu, Jianli 170‑LB
Noble, Earl G. 5‑LB
Nobrega, Marcelo 118‑LB
Noda, Mitsuhiko 61‑LB
Nomura, Akitoshi 161‑LB
Nomura, Daniel K. 153‑LB
Norby, Barbra 20‑LB
Ntambi, James 147‑LB
Nunez, Derek J. 60‑LB
Ockene, Ira S. 197‑LB
O’Connor-Semmes, Robin L. 60‑LB
Odawara, Masato 61‑LB
O’Farrell, Libbey 38‑LB
Ogawa, Daisuke 178‑LB
Ogura, Atsushi 161‑LB
Oh, Dayoung 127‑LB
Ohta, Yasuharu 209‑LB
Oiso, Yutaka 210‑LB
Okutsu, Mitsuharu 163‑LB
Olausson, Eva A. 10‑LB
Olefsky, Jerrold M. 127‑LB
Olendzki, Barbara 197‑LB
Oleski, Jessica 197‑LB
Oliveira, Alexandre G. 177‑LB
Olsen, Sandra E. 3‑LB
Olver, Dylan 5‑LB
Omura, Chiaki 151‑LB
Onthank, Christine 146‑LB
Ordronneau, Paul 57‑LB
Orentreich, David 182‑LB
Orentreich, Norman 182‑LB
Ostadsharif, Kamal 140‑LB
Ostricˇki, Branko 101‑LB
Otvos, James 20‑LB
Oyadomari, Miho 161‑LB
Oyadomari, Seiichi 161‑LB
Pagoto, Sherry 197‑LB
Pairó, Mar 206‑LB
Palau-Collazo, Miladys 49‑LB
Pan, Sufang 113‑LB
Parikh, Grishma 80‑LB
Parikh, Shamik J. 62‑LB
Park, Chang 42‑LB
Park, Chanmi 110‑LB
Park, Hanjong 42‑LB
Park, Soo-Young 118‑LB
Park, Sung Hee 53‑LB
Parker, Camille 56‑LB
Parra, Esteban 117‑LB
Parrott, Abbey 99‑LB
Pate, Virginia 111‑LB
Patel, Jayesh 211‑LB
Patel, Sanjay 68‑LB
Patsouris, David 127‑LB
Paulmurugan, Ramasamy 200‑LB
Pawar, Taranveer K. 84‑LB
Peffers, Mark 182‑LB
Penckofer, Sue 30‑LB
Perkins, Christopher 55‑LB, 57‑LB
Perkovic, Vlado 73‑LB
Perrone, Carmen 182‑LB
Perry, Caroline 52‑LB, 54‑LB, 55‑LB, 57‑LB, 58‑LB
Peterson, Richard G. 38‑LB
Peyot, Marie-line 176‑LB
Phagoo, Steve B. 93‑LB
Phinney, Stephen D. 25‑LB
Pichotta, Philip 44‑LB
Pileggi, Antonello 136‑LB
Pirags, Valdis 63‑LB
Pollock, Brad 114‑LB
Pongratz, Rebecca L. 208‑LB
Poretsky, Leonid 80‑LB
Port, John 150‑LB
Powell, Blair 99‑LB
Prabhakar, Bellur 133‑LB
Pratley, Richard 54‑LB
Praw, Stephanie S. 126‑LB
Prentki, Marc 176‑LB
Prentki, Raphaël 176‑LB
Price, David 91‑LB
Prigeon, Ronald 192‑LB
Prihandoko, Rudi 211‑LB
Prochazkova, Zdenka 132‑LB
Proietto, Joe 188‑LB
Prokopenko, Inga 119‑LB
Prud’Homme, Denis 193‑LB
Puppala, Sobha 90‑LB
Qu, Liming 116‑LB
Quehenberger, Oswald 127‑LB
Quinn, Laurie 42‑LB
Qureshi, Sheeraz A. 157‑LB
Ra, Ho 13‑LB
Rabasa-Lhoret, Remi 193‑LB
Rabinovitz, Rona 89‑LB
Radichev, Ilian 56‑LB
Rainger, George E. 124‑LB
Ramires, Jose 6‑LB
Ramkumar, Kunka Mohanram 200‑LB
Ramsey, Kathryn M. 151‑LB
Ran, Nina 83‑LB
Ranganath, L. 173‑LB
Rasku, Julie 146‑LB
Rasouli, Neda 86‑LB
Rayfield, Eliot J. 80‑LB
Raymond, Ralph H. 143‑LB, 144‑LB, 145‑LB
Rayner, Nigel W. 116‑LB
Reddivari, Lavanya 90‑LB
Reinhardt, Rickey 55‑LB, 57‑LB
Reiss, Allan 92‑LB
Rendell, Marc 55‑LB
Reusch, Jane 57‑LB
Rewers, Marian J. 94‑LB
Rexrode, Kathryn M. 108‑LB
Rezende, Paulo 6‑LB
Rhodes, Christopher J. 217‑LB
Rice, David 146‑LB
Richards, Louise 24‑LB
Ricordi, Camillo 136‑LB
Riddle, Matthew C. 43‑LB
Rieck, Sebastian 205‑LB
Ried, Janina 119‑LB
Rimm, Eric B. 108‑LB
Ripatti, Samuli 119‑LB
LB63
Roberson, Tamara M. 20‑LB
Roberts, Brian K. 79‑LB
Robertson, R. Paul 143‑LB, 145‑LB
Rodgers Fischl, Andrea 99‑LB
Rodriguez, Maria Antonia 29‑LB
Rodriguez-Diaz, Rayner 207‑LB
Rodriguez-Sosa, Miriam 134-LB
Roggerio, Alessandra 6‑LB
Rohn, Reuben 130‑LB
Rohwedder, Katja 62‑LB
Rosen, Rosen D. 183‑LB
Rosenstock, Julio 68‑LB, 70‑LB
Rotenstein, Lisa 83‑LB
Roy, Anirban 49‑LB
Ruedy, Katrina 92‑LB
Ruiz, Michael A. 12‑LB
Ruzzin, Jerome 193‑LB
Rybin, Denis 121‑LB, 122‑LB
Rypackova, Blanka 132‑LB
Saad, Mario J. 177‑LB
Saad, Sara O. 177‑LB
Saenger, Amy K. 20‑LB
Sakai, Soichi 72‑LB
Sakuma, Kensuke 67‑LB
Sakuma, Toshie 135‑LB
Salas-Fernández, Alejandra 87‑LB
Salazar, Tatiana 11‑LB
Salsali, Afshin 69‑LB, 74‑LB
Sammeth, Michael 201‑LB
Samukawa, Yoshishige 72‑LB
San José Terrón, Patricia 206‑LB
Sanchez-Zamora, Yuriko Itzel 134-LB
Sandhu, Sartaj 166‑LB
Sandoval, Darleen A. 180‑LB
Sarin, Antti-Pekka 119‑LB
Saslow, Laura 25‑LB
Satin, Leslie 204‑LB
Sato, Ryosuke 161‑LB
Savinov, Alexei Y. 56‑LB
Savoye, Mary 88‑LB
Schenk, Simon 162‑LB
Schernthaner, Guntram 63‑LB
Scheys, Joshua 214‑LB
Schmitt, Patricia 99‑LB
Schneider, Kristin L. 197‑LB
Scholl, Theresa O. 96‑LB
Schwartz, Gary 179‑LB
Schwartz, Michael W. 167‑LB
Schwarz, Sarah 42‑LB
Seeley, Randy J. 180‑LB
Seggelke, Stacey A. 86‑LB
Segre, Alexandre 6‑LB
Seino, Susumu 210‑LB, 213‑LB
Sekar, Thillai V. 200‑LB
Sereika, Susan 99‑LB
Sesso, Howard D. 107‑LB
Seymour, Heidi 182‑LB
Shaffer-Hudkins, Emily 31‑LB
Shariat-Madar, Zia 186‑LB
Sharma, Sumit 97‑LB
Shastry, Barkur A. 9‑LB
Shaw, James 28‑LB, 215‑LB
Shaw, Melissa 88‑LB
Shaw, Wayne 76‑LB
Shekiro, Kelly M. 216‑LB
Shelton, Richard C. 33‑LB
Sherr, Jennifer L. 49‑LB
Sherwin, Robert S. 140‑LB
Shiba, Teruo 61‑LB
Shibasaki, Tadao 210‑LB, 213‑LB
Shin, Chan Soo 110‑LB
Shoemaker, Kevin 5‑LB
Shong, Minho 212‑LB
Signal, Matthew 35‑LB
Simcox, Judith 149‑LB
Simms, Patrick 44‑LB
Simon, Jacan 56‑LB
Simrén, Magnus 10‑LB
Sims, Emily K. 187‑LB
Sinclair, Alan 76‑LB
Singer, Britta 16‑LB
Singh, Jaideep 18‑LB
Singh, Rajvir 140‑LB
Singh, S.K. 23‑LB
Singleton, Walter 51‑LB
Skare, Sharon 75‑LB
Skrepnek, Grant H. 82‑LB
Sleigh, Alsion 172‑LB
Sloan, Jeanne M. 93‑LB
Slover, Robert 48‑LB
Smith, Greg 35‑LB, 168‑LB
Smith, Kenneth J. 81‑LB
Smith, Steven R. 184‑LB
Snead, Wanda 78‑LB
Somesh, B.P. 18‑LB
Son, JeeWoong 59‑LB
Sonenberg, Nahum 214‑LB
Song, Yiqing 107‑LB
Sotoudeh, Masoud 140‑LB
Spann, Nathanael J. 127‑LB
Speight, Jane 28‑LB, 47‑LB
Sprandel, Marilia 6‑LB
Steck, Andrea K. 94‑LB
Stefanovski, Darko 144‑LB, 167‑LB, 194‑LB
Stephens, Heather 24‑LB
Stewart, Alex 16‑LB
Stewart, Murray 52‑LB, 54‑LB, 55‑LB, 57‑LB,
58‑LB
Stone, Libby 78‑LB
Storsrud, Stine 10‑LB
Strawbridge, Rona J. 116‑LB
Striker, Gary E. 157‑LB, 80‑LB
Strunz, Celia 6‑LB
Stull, Natalie 187‑LB
Sturmer, Til 111‑LB
Sum, Chee Fang 26‑LB
SUMMIT 116‑LB
Sun, Qi 108‑LB
Sun, Weiping 77‑LB
Sun, Zilin 105‑LB
Sunil, V. 18‑LB
Surakka, Ida 119‑LB
Survant, Libby 78‑LB
Susuki, Yosuke 209‑LB
Sutter, Jennifer A. 95‑LB
Swamy, Shobha 80‑LB
Sweeney, Grace 24‑LB
Szczepaniak, Edward W. 155‑LB
Szczepaniak, Lidia S. 155‑LB
Tabrizian, Tahmineh 186‑LB
Taegtmeyer, Heinrich 4‑LB
Taguchi, Akihiko 209‑LB
Tai, Andrew C. 185‑LB
Takahara, Kazuna 161‑LB
Takahashi, Harumi 210‑LB, 213‑LB
Takahashi, Toshimasa 213‑LB
Takeuchi, Koji 67‑LB
Talukdar, Saswata 127‑LB
Tam, Sidney 185‑LB
Tamai, Ikumi 72‑LB
Tamboli, Robyn A. 148‑LB
Tamborlane, William V. 49‑LB, 88‑LB
Tamler, Ronald 80‑LB
Tanabe, Katsuya 209‑LB
Tanenberg, Robert J. 50‑LB, 95‑LB
Tanizawa, Yukio 209‑LB
Tao, Ya-Xiong 189‑LB, 191‑LB
Tasali, Esra 169‑LB
Tchernof, André 195‑LB
Tehan, Ben 211‑LB
Téllez, Noelia 206‑LB
Terami, Naoto 178‑LB
Terami, Takahiro 178‑LB
Terauchi, Yasuo 61‑LB
Tersey, Sarah A. 187‑LB
Thankamony, Ajay 172‑LB
Thatava, Tayaramma 203‑LB
Theuerkauf, Anett 62‑LB
Thomas, Joshua 139‑LB
Thorleifsson, Gudmar 119‑LB
Tichy, Eileen M. 49‑LB
Tinahones, Francisco J. 198‑LB
Tirri, Lauren 80‑LB
Tischkau, Shelley 181‑LB
Tobacman, Joanne K. 158‑LB
Tobe, Kazuyuki 61‑LB
Todd, Jennifer 120‑LB
Tong, Xin 217‑LB
Tonne, Jason 135‑LB
Toplek, Goran 101‑LB
Torres, Jason M. 117‑LB
Toschi, Elena 159‑LB
Touma, Carol 169‑LB
Trautmann, Michael 59‑LB
Tsalikian, Eva 92‑LB
Tso, Patrick 156‑LB
Tsujihata, Yoshiyuki 67‑LB
Turksoy, Kamuran 42‑LB
Tzur, Dorit 89‑LB
Uenishi, Eitai 210‑LB
Umland, Oliver 136‑LB
Unterman, Terry G. 158‑LB
Urbanová, Jana 132‑LB
Uribarri, Jaime 80‑LB
Usiskin, Keith 73‑LB, 76‑LB
Vaag, Allan 172‑LB
Valdearcos, Martin 153‑LB
Valledares-Salagado, Adan 117‑LB
Van Bavel, Bert 193‑LB
Van Cauter, Eve 169‑LB
Van Iperen, Erik P. 116‑LB
Van Zuydam, Natalie 116‑LB
Vanamala, Jairam 90‑LB
Vander Heiden, Matthew G. 208‑LB
Vassy, Jason L. 121‑LB
Vath, James E. 188‑LB
Venkataranganna, M.V. 18‑LB
Vercruysse, Frank 65‑LB
Vergani, Andrea 136‑LB
Vernon, Marlo 32‑LB
Vijapurkar, Ujjwala 73‑LB, 76‑LB
Vilches-Flores, Alonso 134-LB
Vilsbøll, Tina 173‑LB
Vlachopoulou, Efthymia 116‑LB
Vlassara, Helen 80‑LB, 157‑LB
Voight, Benjamin F. 116‑LB
Von Eynatten, Maximilian 2‑LB, 68‑LB
Von Holtey, Maria 19‑LB
Vora, Jiten 47‑LB, 173‑LB
Wada, Jun 178‑LB, 183‑LB
Walder, Ken 138‑LB
Walker, Lucy 124‑LB
Wallen, Taylor 204‑LB
LB64
Wallis, Diane 30‑LB
Wamhoff, Brian 139‑LB
Wan, Gang 113‑LB
Wang, Binhuan 29‑LB
Wang, Cecilia L. 86‑LB
Wang, Chen-Pin 114‑LB
Wang, Chun 181‑LB
Wang, Fei 156‑LB
Wang, Jianxin 17‑LB
Wang, Lin 163‑LB
Wang, Lu 107‑LB
Wang, Xiangfei 41‑LB
Wang, Ying 77‑LB
Wang, Yunjiao 86‑LB
Waring, Molly 197‑LB
Wasserman, David H. 158‑LB, 167‑LB
Waters, Thaddeus P. 98‑LB
Watkins, Steven M. 127‑LB
Weinzimer, Stuart A. 49‑LB, 92‑LB
Weiss, Elizabeth 146‑LB
Wencker, Detlef 140‑LB
Weyman, Kate 49‑LB
Whately-Smith, Caroline 47‑LB
White, Amanda T. 162‑LB
White, Michael G. 215‑LB
Whited, Matthew C. 197‑LB
Wilkinson, Helen 24‑LB
Willems, Sara M. 116‑LB
Willenborg, Christina 119‑LB
Williams, Brandon 148‑LB
Williams, Mark 56‑LB
Williams, Stephen 16‑LB
Wilson, Craig 66‑LB
Wilson, Darrell M. 37‑LB
Wilson, James G 122‑LB
Winkler, Thomas W. 119‑LB
Wisherd, Chris 146‑LB
Witkowski, Piotr 118‑LB
Woerle, Hans-Juergen 2‑LB, 68‑LB, 69‑LB, 71‑LB,
74‑LB
Woo, Vincent 73‑LB
Woodlief, Tracey 190‑LB
Woods, Stephen C. 156‑LB, 180‑LB
Woodward, Mark 80‑LB
Wu, Qiang 95‑LB
Wylie-Rosett, Judith 29‑LB
Xie, John 65‑LB
Xie, Rongrong 113‑LB
Xie, Xiangyang 184‑LB
Xiong, Keming 147‑LB
Xu, Aimin 185‑LB
Xu, Allison W. 153‑LB
Xu, Can-Xin 181‑LB
Xu, Jianfeng 127‑LB
Xu, Min 156‑LB
Yabuki, Chiori 67‑LB
Yamaguchi, Jun-ichi 72‑LB
Yamamoto, Masayoshi 209‑LB
Yamazaki, Tsutomu 61‑LB
Yan, Yuanqing 11‑LB
Yan, Zhen 163‑LB
Yanek, Lisa R. 122‑LB
Yang, Fred 52‑LB, 55‑LB, 58‑LB
Yang, Guang-Ran 113‑LB
Yang, Jiayue 105‑LB
Yap, Mee Li 26‑LB
Yarborough, OrLando 208‑LB
Yarchoan, Mark 83‑LB
Yates, Clara M. 124‑LB
Ye, June 54‑LB, 57‑LB
Yeo, Giles 172‑LB
Yip, Shelley 168‑LB, 35‑LB
Yoon, Kun-Ho 65‑LB
Yoshimura, Akihiko 128‑LB
Younce, Craig W. 170‑LB
Young, Andrew A. 171‑LB
Young-Hyman, Deborah L. 32‑LB
Yu, Kin-Hung P. 79‑LB
Yu, Liping 94‑LB
Yu, Maria 106‑LB
Yuan, Mingxia 113‑LB
Yuan, Shenyuan 113‑LB
Yubero-Serrano, Elena M. 80‑LB
Yue, Jessica T. 152‑LB
Zgibor, Janice C. 81‑LB
Zhang, Hui 184‑LB
Zhang, Kehao 179‑LB
Zhang, Lu 102‑LB
Zhang, Sarah X. 17‑LB
Zhang, Yang 179‑LB
Zhang, Yurong 102‑LB
LB65
Zhang, Zhenzhen 102‑LB
Zhao, Ruxing 129‑LB
Zhao, Shangang 176‑LB
Zhao, Xiaojian 208‑LB
Zhao, Xiaolong 41‑LB
Zhong, Yimin 17‑LB
Zhou, Qiong L. 184‑LB
Zhu, Liangxiang 113‑LB
Zhuang, Ning 113‑LB
Ziemen, Monika 43‑LB
ABSTRACT Author DISCLOSURE INFORMATION
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Abbas, Zulfiqarali G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Abbasakoor, Noormuhammad пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Abdelmoneim, Sahar S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Abdi, Reza пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Abdulkarim, Baroj пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ables, Gene P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Abraham, Varghese пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Abuaysheh, Sanaa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Abumrad, Naji N. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Agarwal, Nutan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Aggarwal, Parul пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ahima, Rexford S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ahluwalia, Rupa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ahmann, Andrew пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Medtronic, Inc.
AhrГ©n, Bo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: GlaxoВ­SmithВ­Kline; Consultant: GlaxoВ­SmithВ­
Kline
Akanuma, Yasuo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Sanwa Kagaku Kenkyusho Co., Ltd
Aldibbiat, Ali пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Alejandro, Emilyn пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Alejandro, Rodolfo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Alexander, Veronica J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Isis Pharmaceuticals, Inc.; Stock/Shareholder:
Isis Pharmaceuticals, Inc.
Almaca, Joana пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Alturaifi, Husain пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Alves, Tiago пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Amatya, Christina пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ambrosius, Walter T. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
An, Ping пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Andel, Michal пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Anderson, Robert J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Andrews, Jeanette S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Andrews, Susan M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Andrikopoulos, Sof пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Anilkumar, D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Anseth, Kristi S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Antoun, Joseph пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Anup, O. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Appelhans, Brad пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Arakawa, Hiroshi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Archibald, Lennox K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Arias, Pablo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: AstraZeneca Pharmaceuticals, Boehringer
Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb
Company, Eli Lilly and Company, Novartis PharmaceuВ­
ticals Corporation, Roche Diagnostics
Armando, Aaron пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Armstrong, David пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Arnold, Myrtha пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Arya, Rector пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Asare, Isaac B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Г…svold, BjГёrn Olav пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Attvall, Stig пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Aubert, Gregory пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Augie, Ines пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Auwerx, Johan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Awan, Fazli R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ayala, Julio E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Aye, Tandy пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Krikorjan
Azzi, Jamil R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Babor, Richard пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bagarolli, Renata A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bahn, Gideon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bailey, Clifford J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bailey, Kathleen A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bailey, Timothy S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bakris, George пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Janssen Pharmaceuticals, Inc.
Baldi, Simona пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Balis, Dainius A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Bandyopadhyay, Gautam пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bansal, Vivek пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Barbaresso, Rebecca пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Barbier, Maryse пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Barendse, Shalleen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: GlaxoВ­SmithВ­Kline
Barnea-Goraly, Naama пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Baron, Alain пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Board Member: Elcelyx Therapeutics, Inc.; Employee: ElceВ­
lyx Therapeutics, Inc.; Stock/Shareholder: Elcelyx
Therapeutics, Inc.
Barone, Francesca пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
RELATIONSHIP/COMPANY
Bass, Joseph T. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Basterra-Gortari, Francisco Javier пїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Basu, Ananda пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Basu, Rita пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Batra, Manav пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bauer, Tim пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: SomaLogic, Inc.
Bayona, Zarana пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bayrak, Elif Seyma пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Beban, Grant пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Beck, Roy пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Animas Corporation; Research Support: Sanofi
Becker, Dorothy J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Beekman, Marian пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Begley, Joe пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bell, Graeme I. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Below, Jennifer пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Benasi, Kari пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Benninger, Richard K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Benoit, Stephen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bequette, B. Wayne пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bergenstal, Richard M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Medtronic, Inc.
Berggren, Per-Olof пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bergman, Richard N. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Amylin Pharmaceuticals, Inc.; Consultant:
Amylin Pharmaceuticals, Inc., Bristol-Myers Squibb
Company, Eli Lilly and Company, Tethys; Speaker’s
Bureau: Merck; Stock/Shareholder: Tethys
Bernal-Lopez, Rosa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bernal-Mizrachi, Ernesto пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bernard, Abigail B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bes-Rastrollo, Maira пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Beserab, Anatole пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: FibroGen, Inc.
Bhanot, Sanjay пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Isis Pharmaceuticals, Inc.; Stock/Shareholder:
Isis Pharmaceuticals, Inc.
Bhargava, Tina пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bhattacharyya, Sumit пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bhatwadekar, Ashay D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bielak, Lawrence F. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Birnbaum, Morris J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bishop, Michael пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline
Bizet, Florence пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Sanofi
BjГёrgaas, Marit R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Blackman, Brett пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Blandino-Rosano, Manuel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Blangero, John пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Blankfard, Martin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: ALPCO Diagnostics
Bode, Bruce пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Atlanta Diabetes Associates, Janssen
Pharmaceuticals, Inc., Medtronic, Inc.; Speaker’s
Bureau: Atlanta Diabetes Associates
Bogle, Allyson пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Bristol-Myers Squibb Company; Stock/Shareholder: Bristol-Myers Squibb Company
Bolli, Geremia B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Sanofi; Consultant: Novartis PharmaceutiВ­
cals Corporation, Sanofi; Speaker’s Bureau: Eli Lilly
and Company
Booth, Michael пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bottu, Guy пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bottum, Kathleen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bouchard, Jonathan R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Novo Nordisk, Inc.; Stock/Shareholder: Novo
Nordisk, Inc.
Boucher, Jackie L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Boulton, Michael E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bracy, Deanna P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Brennand, Cath пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Brockway, Robert пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Data Science International
Broedl, Uli C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
Broussard, Josiane L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Brown, Alastair J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Bryce, Cindy L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Buckingham, Bruce пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Board Member: Medtronic Inc., Sanofi; Research Support:
Medtronic, Inc.
Buckley, Christopher D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Buenaventura, Jefi Jaustine пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Buring, Julie E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Burkey, Jennifer пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Isis Pharmaceuticals, Inc.; Stock/Shareholder:
Isis Pharmaceuticals, Inc.
Burn, Paul пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Diamedica, Inc.
Busch, Andrew M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Buse, John пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Amylin Pharmaceuticals, Inc., Andromeda BioВ­
tech, Ltd., AstraZeneca Pharmaceuticals LP, Bayhill
Therapeutics, Inc., Becton, Dickson and Company
LB66
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Research Laboratories, Bristol-Myers Squibb ComВ­
pany, Catabasis, Cebix, Inc., Diartis Pharmaceuticals,
Elcelyx Therapeutics, Inc., Eli Lilly and Company, ExsuВ­
lin Corporation, Genentech, Inc., GI Dynamics, Inc.,
Halozyme Therapeutics, Hoffman La Roche, Inc.,
Johnson & Johnson Services, Inc., LipoScience, Inc.,
Merck, Metabolic Solutions Development Co., MetabВ­
olon, Inc., Novan, Inc., Novella, Novo Nordisk, Inc.,
Orexigen Therapeutics, Inc., Rhythm Pharmaceuticals,
Sanofi, Spherix, Inc., TransPharma Medical, Veritas,
Verva; Research Support: Abbott Laboratories, Inc.,
Amylin Pharmaceuticals, Inc., Andromeda Biotech,
Ltd., AstraZeneca Pharmaceuticals LP, Boehringer
Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb
Company, Eli Lilly and Company, GI Dynamics, Inc.,
GlaxoВ­SmithВ­Kline, Halozyme Therapeutics, Hoffman La
Roche, Inc., Johnson & Johnson Services, Inc.,
Medtronic, Inc., Merck, Novo Nordisk, Inc., Orexigen
Therapeutics, Inc., Osiris Therapeutics, Inc., Pfizer,
Inc., Sanofi, Takeda Pharmaceutical Company, Ltd.,
Tolerx, Inc.
Busik, Julia V. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Busta, Agustin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Byrn, Mary пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cade, Brian пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cai, Weijing пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Caicedo, Alejandro пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Caldwell, Jody пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cameron, Fraser пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Camisasca, Riccardo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Global Research & Development CenВ­
ter, Inc.
Camp, Anne пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Candelaria, Karla пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Canney, Lori пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Biodel, Inc.; Stock/Shareholder: Biodel, Inc.
Canovatchel, William пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Caprio, Sonia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cardona, Fernando пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Carpentier, AndrГ© пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Carr, Molly C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Carria, Lori R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Carter, Lauren пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Carvalho, Ana пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Carvalho, Bruno M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Casella-Filho, Antonio пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Casteilla, Louis пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Castellano-Castillo, Daniel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Catalano, Patrick пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cato, Allison пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cefalu, William T. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: AstraZeneca Pharmaceuticals; Consultant:
AstraZeneca Pharmaceuticals, Bristol-Myers Squibb
Company, Halozyme Therapeutics, Intarcia TherapeuВ­
tics, Inc., Johnson & Johnson Services, Inc., Lexicon
Pharmaceuticals, sanofi-aventis; Research Support:
AstraZeneca Pharmaceuticals, Bristol-Myers Squibb
Company, Eli Lilly and Company, GlaxoВ­SmithВ­Kline,
Johnson & Johnson Services, Inc., Lexicon PharmaВ­
ceuticals, MannKind Corporation
Cengiz, Eda пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cerna, Marie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cha, Eunme пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chadwick, Thomas пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chakrabarti, Subrata пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chalamandaris, Alexandros-Georgios пїЅпїЅпїЅпїЅ Employee: Bristol-Myers Squibb Company; Stock/Shareholder: Bristol-Myers Squibb Company
Chambers, Adam P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Ethicon EndoSurgery, Inc.
Chan Lee, Won пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: IMS Health, Inc.
Chapple, Olivia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Charles, Matt пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Diamedica, Inc.
Charron-Prochownik, Denise пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chase, Geoffery пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chase, Peter пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chaudhry, Zunaira пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chaudhuri, Ajay пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Alice пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Angela пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Chen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Danny пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Pfizer, Inc.; Stock/Shareholder: Pfizer, Inc.
Chen, Guanje пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Julie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Li пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Lihong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline
Chen, Rony пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
RELATIONSHIP/COMPANY
Chen, Shyh-Huei пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Wei-Min пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Xinhua пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Xue пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chen, Yingxian пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cheng, Lei пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cheng, Peiyao пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chernoff, Arthur пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chiamvimonvat, Nipavan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chimen, Myriam пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chino, Yukihiro пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chism, Jack P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Chittoor, Geetha пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Choi, Hyung Jin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Choi, In Young пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Choi, Jessica пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Choi, John пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Choi, Min Jeong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Choi, Soomin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chu, Qingwei пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chuang, Eunice Y. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chun, Kelly Y. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chung, Hyo Kyun Chung пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chung, Sookja K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Chung, Stephen S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ciardella, Antonio пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cinar, Ali пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cinar, Resat пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cipriani, Yolanda пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cirkel, Deborah пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Cistrone, Monica пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Clark, Michelle пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Clemente-Postigo, Mercedes пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Clements, Mark пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Clements, Ronald H. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Clinton, Paula пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Close, Kelly пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cmreˇcnjak, Jasna ��������������������������������� Disclosed no conflict of interest.
Cnop, Miriam пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cobelli, Claudio пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Johnson & Johnson Services, Inc.;
Research Support: Dexcom, Inc., Insulet Corporation
Coen, Paul M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cohen, Neale ��������������������������������������� Advisory Panel: Eli Lilly and Company; Speaker’s Bureau:
AstraZeneca Pharmaceuticals LP, Eli Lilly and ComВ­
pany, Medtronic, Inc., Novartis Pharmaceuticals CorВ­
poration, Novo Nordisk A/S, Sanofi
Collins, Andrew W. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Collins, Jon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline
Comuzzie, Anthony G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Connor, Tim пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Coskun, Tamer пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company; Stock/Shareholder: Eli
Lilly and Company
Cowan, David пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline
Cox, Nancy J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cox, Rachel M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Crawford, Sybil пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Crooke, Rosanne M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Isis Pharmaceuticals, Inc.; Stock/Shareholder:
Isis Pharmaceuticals, Inc.
Cruz, Miguel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cundy, Tim пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Cunnion, Kenji M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
’ c’ , Korana ������������������������������������������ Disclosed no conflict of interest.
Cri
Curran, Joanne E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Currie, Craig J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Czeczor, Juliane K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
D’Alessio, David A. ������������������������������ Disclosed no conflict of interest.
D’Eramo Melkus, Gail �������������������������� Disclosed no conflict of interest.
Da Silva, Alexandre A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Da Silva, Jussara M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Da Silva, Natalia T. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dalal, Krishna пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dalla Man, Chiara пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dandona, Paresh пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Daniels, Mark пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Das, Nibhriti пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Das, Swapan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dash, Ajit пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Daubenmier, Jennifer J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Davies, Melanie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Boehringer Ingelheim Pharmaceuticals,
Inc., Eli Lilly and Company, Merck Sharp & Dohme,
Corp., Novartis Pharmaceuticals Corporation, Novo
LB67
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Nordisk, Inc., Roche Pharmaceuticals, sanofi-aventis;
Consultant: Boehringer Ingelheim Pharmaceuticals,
Inc., Eli Lilly and Company, Merck Sharp & Dohme,
Corp., Novartis Pharmaceuticals Corporation, Novo
Nordisk, Inc., Roche Pharmaceuticals, sanofi-aventis;
Research Support: Eli Lilly and Company, GlaxoВ­SmithВ­
Kline, Merck Sharp & Dohme, Corp., Novartis PharmaВ­
ceuticals Corporation, Novo Nordisk, Inc., Pfizer, Inc.,
sanofi-aventis; Speaker’s Bureau: Boehringer
Ingelheim Pharmaceuticals, Inc., Eli Lilly and ComВ­
pany, Merck Sharp & Dohme, Corp., Novartis PharmaВ­
ceuticals Corporation, Novo Nordisk, Inc., Roche PharВ­
maceuticals, sanofi-aventis
Davis, Cecilia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Davis, Dianne пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
De Aguiar, Renata B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
De la Fuente, Carmen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
De Souza, Errol пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Biodel, Inc.; Stock/Shareholder: Biodel, Inc.
De Zeeuw, Dick пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Astellas, Takeda Pharmaceutical ComВ­
pany, Ltd.; Consultant: Abbott Laboratories, Abbvie,
Inc., Hemocue, Johnson & Johnson Services, Inc.,
Novartis Pharmaceuticals Corporation, Reata PharmaВ­
ceuticals, Inc., Vitae Pharmaceuticals; Research Support: Abbott Laboratories, Abbvie, Inc., Hemocue,
Johnson & Johnson Services, Inc., Novartis PharmaВ­
ceuticals Corporation, Reata Pharmaceuticals, Inc.,
Vitae Pharmaceuticals
Deering, Tye пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
DeFronzo, Ralph A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Amylin Pharmaceuticals, Inc., Boehringer
Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb
Company, Janssen Biotech, Inc., Novo Nordisk, Inc.,
Takeda Pharmaceutical Company, Ltd.; Other Relationship: Amylin Pharmaceuticals, Inc., Takeda PharmaceuВ­
tical Company, Ltd.; Speaker’s Bureau: Dekoven, Mitch­
ell, Novo Nordisk, Inc.; Consultant: IMS Health, Inc.
Del Prato, Stefano пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: AstraZeneca Pharmaceuticals LP, BoehВ­
ringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers
Squibb Company, Eli Lilly and Company, GlaxoВ­SmithВ­
Kline, Intarcia Therapeutics, Inc., Janssen PharmaceuВ­
ticals, Inc., Merck, Novartis Pharmaceuticals CorporaВ­
tion, Novo Nordisk A/S, Roche Pharmaceuticals,
Sanofi, Takeda Global Research & Development CenВ­
ter, Inc.; Research Support: Bristol-Myers Squibb
Company, Merck, Novartis Pharmaceuticals CorporaВ­
tion, Sanofi, Takeda Global Research & Development
Center, Inc.; Speaker’s Bureau: Novartis Pharmaceuti­
cals Corporation
Delebecque, Fanny пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Demozay, Damien пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dennis, Edward пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Derazne, Estella пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Desai, Mehul пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Deschamps, Ketra пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company
Despa, Florin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Despa, Sanda пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dessapt, Cecile пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dey, Adwitia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dhindsa, Sandeep пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dhir, Ravindra пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Diamant, Michaela пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Diaz, Ana пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Diennet, Marine пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
DiPilato, Lisa M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dixit, Snehil пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dobbins, Robert L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline
Dohi, Taeko пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dolan, Lawrence M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dominguez, James пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dominguez, Ligia J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dong, Fran пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dong, Hua пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dong, Jessica пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dong, Xinyuan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dougan, Michael пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Doyle, Todd пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Draznin, Boris пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Novo Nordisk, Inc., Sanofi
Dronavalli, Suma пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dube, Simmi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dubis, Gabriel S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Duckworth, William пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dugan, Colleen E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Duggirala, Ravindranath пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dugi, Klaus A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
RELATIONSHIP/COMPANY
Dunger, David B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dupuis, JosГ©e пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
DurГЎn-Garcia, Santiago пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Other Relationship: Abbott Diabetes Care, AstraZeneca
Pharmaceuticals LP, Boehringer Ingelheim PharmaceuВ­
ticals, Inc., Bristol-Myers Squibb Company, Eli Lilly
and Company, Janssen Pharmaceuticals, Inc., MannВ­
Kind Corporation, Merck Sharp & Dohme Limited,
Novartis Pharmaceuticals Corporation, Novo Nordisk
A/S, Pfizer, Inc., Roche Pharmaceuticals, Sanofi,
Servier, Takeda Pharmaceutical Company, Ltd.
Dushay, Jody пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Dziura, James пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Eby, Elizabeth пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company
Eckert, Emily A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Edelman, Steven V. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Eli Lilly and Company; Consultant: Abbott
Laboratories, Inc., Boehringer Ingelheim PharmaceutiВ­
cals, Inc., Bristol-Myers Squibb Company, Dexcom,
Inc., Merck, Novo Nordisk, Inc., Sanofi, Tandem DiaВ­
betes Care; Speaker’s Bureau: Eli Lilly and Company
Edukulla, Ramakrishna пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Edwy, Marjan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Novo Nordisk, Inc.; Stock/Shareholder: Novo
Nordisk, Inc.
Eggen, Silje A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Eguchi, Jun пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Eizirik, Decio L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
El Khatib, Moustafa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
El-Remessy, Azza B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Elango, Bhakkiyalakshmi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Elder, Deborah пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ellefson, Jacob пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Elliot, Sharon J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Emanuele, Mary Ann пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Emanuele, Nicholas пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Emmett, Matt пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Errazuriz Cruzat, Isabel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Escobedo, Jorge пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Espinosa-Heidmann, Deigo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ethridge, John K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Evans, Marc пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Merck Sharp & Dohme Limited, Novartis
Pharmaceuticals Corporation, Novo Nordisk A/S,
Sanofi; Research Support: Novo Nordisk A/S, Sanofi
Evans, Mark L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Cellnovo, Medtronic, Inc., Roche PharmaВ­
ceuticals; Speaker’s Bureau: Abbott Diabetes Care;
Stock/Shareholder: Cellnovo
Evans-Molina, Carmella пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fang, Donghong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fang, Yixin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Farfel, Alon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Farhy, Leon S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Farook, Vidya S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Farooq, Amina пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Favarato, Desiderio пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Feferman, Leonid пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fernandez-Garcia, Diego пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ferrannini, Ele пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Astellas Pharma US, Inc., AstraZeneca
Pharmaceuticals, Bristol-Myers Squibb Company,
Boehringer Ingelheim Pharmaceuticals, Inc., GlaxoВ­
SmithВ­Kline, Halozyme Therapeutics, Janssen PharmaВ­
ceuticals, Inc., Merck Sharp & Dohme Limited, Sanofi,
Takeda Pharmaceuticals U.S.A., Inc.; Research Support: Boehringer Ingelheim GmbH & Co. KG, Eli Lilly
and Company, Merck Sharp & Dohme Limited
Ferreira, Teresa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fineman, Mark пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Elcelyx Therapeutics, Inc.; Stock/Shareholder:
Elcelyx Therapeutics, Inc.
Finkelstein, Joseph пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fiorina, Paolo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fisher, Deirdre пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fisher, Ffolliott M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Flanagan, Daniel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fleck, Penny пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Global Research & Development CenВ­
ter, Inc.
Florez, Jose пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Floyd, Elizabeth пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Flynn, Charles R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Forga, Lluis пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fotino, Carmen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fouda, Abdelrahman пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fouqueray, Pascale пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Fowler, Sharon P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Foygel, Kira пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Franco, Marietta пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: FibroGen, Inc.
Franz, Marion J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
LB68
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Frascerra, Silvia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Friedberg, Jennifer пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Friedman, David пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Frier, Brian M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Eli Lilly and Company, Johnson & Johnson
Services, Inc., Merck Sharp & Dohme Limited, Novo
Nordisk, Inc., Roche Pharmaceuticals, Sanofi; Speaker’s Bureau: Boehringer Ingelheim GmbH & Co. KG, Eli
Lilly and Company, Merck Sharp & Dohme Limited,
Novo Nordisk, Inc.
Fryburg, David A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Stock/Shareholder: Pfizer, Inc.
Fu, Wuxia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Isis Pharmaceuticals, Inc.; Stock/Shareholder:
Isis Pharmaceuticals, Inc.
Fung, Albert пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Gaddy, James R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Galinier, Anne пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gallwitz, Baptist пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: AstraZeneca Pharmaceuticals LP, BoehВ­
ringer Ingelheim GmbH & Co. KG, Bristol-Myers
Squibb Company, Eli Lilly and Company, Merck,
Novartis Pharmaceuticals Corporation, Novo Nordisk,
Inc., Roche Pharmaceuticals, Sanofi, Takeda PharmaВ­
ceutical Company, Ltd.; Other Relationship: AstraZenВ­
eca Pharmaceuticals LP, Boehringer Ingelheim GmbH
& Co. KG, Bristol-Myers Squibb Company, Eli Lilly and
Company, Merck, Novartis Pharmaceuticals CorporaВ­
tion, Novo Nordisk, Inc., Roche Pharmaceuticals,
Sanofi, Takeda Pharmaceutical Company, Ltd.
Gamazon, Eric пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Garcia, Anna пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Garduno Garcia, Jose de Jesus пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Garg, Satish K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Medtronic, Inc.
Garhyan, Parag пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company; Stock/Shareholder: Eli
Lilly and Company
Garrido-Sanchez, Lourdes пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Garrison, Herbert G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gassmann-Mayer, Cristiana пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Gauthier, Marie-Soleil пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gaziano, J. Michael пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ge, Junbo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gea, Alfredo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Geary, Richard пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Isis Pharmaceuticals, Inc.; Stock/Shareholder:
Isis Pharmaceuticals, Inc.
Gelwicks, Steve пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Community Hospitals of Indianapolis/CommuВ­
nity Health Network (Spouse/Partner), Eli Lilly and
Company
Genders, Amanda J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Geng, Dawei пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
George, Tom пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gerich, John пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Boehringer Ingelheim GmbH & Co. KG, Eli
Lilly and Company, Johnson & Johnson Services, Inc.,
Sanofi; Speaker’s Bureau: AstraZeneca Pharmaceuti­
cals LP, Boehringer Ingelheim GmbH & Co. KG, BristolMyers Squibb Company, Eli Lilly and Company, JohnВ­
son & Johnson Services, Inc., Merck
Ghanim, Husam пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ghosh, Sangeeta пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ghosh, Sujoy пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gibbs, Joanna пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Glass, Chirstopher пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Glass, Leonard C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company; Stock/Shareholder: Eli
Lilly and Company
GlavaЕЎ, Edgar пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Glynn, Robert J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gnudi, Luigi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Goel, Anuj пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gokhale, Mugdha пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Merck
Goldman, Veronica пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gong, Zhenwei пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Goodpaster, Bret пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Goodyear, Laurie J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
GradiЕЎer, Marina пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Graf, Rolf пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Graham, Mark J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Isis Pharmaceuticals, Inc.; Stock/Shareholder:
Isis Pharmaceuticals, Inc.
Grant, Maria B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Grassi, Fabio пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Converge Biotech, Inc.
Gray, Chris пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Green, Kelly пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gregg, Brigid пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Grenier-Larouche, Thomas пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Griebel, Thasso пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Griffen, Steven C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Bristol-Myers Squibb Company; Stock/Shareholder: Bristol-Myers Squibb Company
RELATIONSHIP/COMPANY
GrisГ©, Kenneth N. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Guddattu, Vasudevan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Guo, Xiuqing пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gupta, S.K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Gutierrez-Juarez, Roger пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Guyer, Katherine M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ha, Yong-Chan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Habata, Yugo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Hach, Thomas пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
Haefner, Paul пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Data Sciences International
Haffner, Steven M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hagan, Scott пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hägg, Sara ������������������������������������������� Disclosed no conflict of interest.
Hair, Pamela пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hale, Daniel E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hall, Ben пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hall, John E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hamdy, Osama пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hammer, Marilyn J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hammock, Bruce пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Han, Jennifer Y. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hanis, Craig L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hanley, Anthony J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hansen, Liz-Iren пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hantel, Stefan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
Hara, Manami пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Harbord, Nikolas пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hardee, Sandra D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hardwick, Christine пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company
Hardy, Thomas A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company; Stock/Shareholder: Eli
Lilly and Company
Harris, Stewart пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: AstraZeneca Pharmaceuticals, BristolMyers Squibb Company, Boehringer Ingelheim PharВ­
maceuticals, Inc., Eli Lilly and Company, Janssen
Pharmaceuticals, Inc., Novo Nordisk, Inc., Sanofi,
Takeda Pharmaceutical Company, Ltd.; Research Support: Merck, Novo Nordisk, Inc., Sanofi; Speaker’s
Bureau: AstraZeneca Pharmaceuticals, Bristol-Myers
Squibb Company, Boehringer Ingelheim PharmaceutiВ­
cals, Inc., Eli Lilly and Company, Novo Nordisk, Inc.,
Sanofi
Harris, Todd пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hartiala, Jaana пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hatanaka, Masayuki пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hawkins, Matthew пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hawkins, Meredith пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hayward, Anthea A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hecht, Frederick M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hehnke, Uwe пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
Heise, Tim пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Boehringer Ingelheim GmbH & Co. KG,
Novo Nordisk, Inc.; Employee: Profil Institute for CliniВ­
cal Research, Inc.; Research Support: Astellas Pharma
US, Inc., Becton, Dickinson and Company, Biocon,
Boehringer Ingelheim GmbH & Co. KG, Danse PharВ­
maceuticals, Eli Lilly and Company, Evolva, Hoffman
La Roche, Inc., Johnson & Johnson Services, Inc.,
Lundbeck, Inc., Novo Nordisk, Inc., Noxxon, Sanofi,
SkyePharma; Speaker’s Bureau: Boehringer Ingelheim
GmbH & Co. KG, Novo Nordisk, Inc.; Stock/Shareholder: Profil Institute for Clinical Research, Inc.
Helbling, Nicole L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Heller, Simon R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Lifescan Animas, Inc., Eli Lilly and Company,
Novo Nordisk, Inc., Sanofi
Hellmann, Pattie H. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Heneberg, Petr пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Henry, Robert R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Amgen, Inc., AstraZeneca PharmaceutiВ­
cals LP, Boehringer Ingelheim Pharmaceuticals, Inc.,
Bristol-Myers Squibb Company, Daiichi-Sankyo, Inc.,
Elcelyx Therapeutics, Inc., Eli Lilly and Company,
Genentech, Inc., Gilead Sciences, Inc., Intarcia TheraВ­
peutics, Inc., Janssen Pharmaceuticals, Inc., Johnson
& Johnson Services, Inc., Merck, Novo Nordisk, Inc.,
Roche Pharmaceuticals, Sanofi; Consultant: BoehВ­
ringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and
Company, Genentech, Inc., Gilead Sciences, Inc., IntВ­
arcia Therapeutics, Inc., Isis Pharmaceuticals, Inc.,
Novo Nordisk, Inc., Sanofi; Research Support: BristolMyers Squibb Company, AstraZeneca PharmaceutiВ­
cals, Eli Lilly and Company, Medtronic, Inc., Sanofi
Herman, Mark A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Herman, William пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hernandez, Javier пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: National Cancer Institute
Hershey, Tamara пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
LB69
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Hess, Rachel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Highland, Heather M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hirshman, Michael F. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hivert, Marie France пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hockey, Andrew пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Sanofi; Stock/Shareholder: Sanofi
Hod, Moshe пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hodge, Rebecca J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Holliday-White, Kimberly пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Data Sciences International
Holterman, Mark пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Home, Philip D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: AstraZeneca Pharmaceuticals, BristolMyers Squibb Company, GlaxoВ­SmithВ­Kline, Johnson &
Johnson Services, Inc., Merck Sharp & Dohme LimВ­
ited, Novo Nordisk A/S, Roche Diagnostics, Roche
Pharmaceuticals, Sanofi, SkyePharma, Takeda PharВ­
maceutical Company, Ltd.; Research Support: AstraВ­
Zeneca Pharmaceuticals, Bristol-Myers Squibb ComВ­
pany, Eli Lilly and Company, GlaxoВ­SmithВ­Kline, Novo
Nordisk A/S, Sanofi; Speaker’s Bureau: AstraZeneca
Pharmaceuticals, Bristol-Myers Squibb Company, Eli
Lilly and Company, Merck Sharp & Dohme Limited,
Novo Nordisk A/S
Hompesch, Marcus пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hong, Hyun Jung пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hong, Jaeyoung пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Horikoshi, Momoko пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hottenga, Jouke-Jan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Houmard, Joseph A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hraha, Thomas H. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hsu, Fang-Chi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hu, Frank B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hu, Gang пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Huang, Hui пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Huang, Jennifer L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Huang, Jingyu пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Huang, Jun-Yuan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Huang, Wenyu пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hueb, Whady пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hughes, Thomas E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Zafgen, Inc.; Stock/Shareholder: Zafgen, Inc.
Hunt, Kelly J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Hwang, Sang Youn пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Iatridis, James C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Iglesias, JosГ© пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Igrec, Miljenka пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ikeda, Yasuhiro пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Illien-Junger, Svenja пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Inagaki-Ohara, Kyoko пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Inge, Tom пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Ethicon EndoSurgery, Inc.
Inkster, Berit пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Inoue, Hiroshi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Inzucchi, Silvio E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Amgen, Inc., Boehringer Ingelheim GmbH &
Co. KG, Bristol-Myers Squibb Company, Janssen PharВ­
maceuticals, Inc., Merck, Takeda Pharmaceutical
Company, Ltd.
Irvin, Marguerite R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ismail-Beigi, Faramarz E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Novo Nordisk, Inc.; Research Support: Novo
Nordisk, Inc.; Stock/Shareholder: Thermalin Diabetes,
LLC.
Ito, Chikako ������������������������������������������ Consultant: Ono Pharmaceutical Co., Ltd.; Speaker’s
Bureau: Eli Lilly Japan, Mitsubishi Tanabe PharmaВ­
ceutical Corporation, Ono Pharmaceutical Co., Ltd.,
Sanwa Kagaku Kenkyusho Co., Ltd., Shionogi, Inc.
Ito, Ryo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Iwamoto, Yasuhiko ������������������������������� Speaker’s Bureau: Chugai Pharmaceutical Co., Ltd., Eli
Lilly Japan, Kissei Pharmaceutical Co., Ltd., Kowa
Pharmaceuticals, Merck Sharp & Dohme Limited, NipВ­
pon Boehringer Ingelheim Co., Ltd., Novartis PharmaВ­
ceuticals Corporation, Novo Nordisk, Inc., Ono PharВ­
maceutical Co., Ltd., Sanofi, Takeda Pharmaceutical
Company, Ltd.
Jackson, Charles V. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Preclinomics
Jackson, Kaleena пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jaeger, Cassie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jaffe, Allan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jagannath, M.R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
James, June R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jang, Hyun-Ju пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jang, Sunmee пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jarres, Russell пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: ALPCO Diagnostics
Jayaraman, Sundararajan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jenkins, Todd пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jenkins-Jones, Sara пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jenkinson, Christopher P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
RELATIONSHIP/COMPANY
Jensen, Majken K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jensen, Richard A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jeong, Ku Bon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jiang, Ling пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jiang, Zhen Y. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jiao, Yang пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jimenez, Monik C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jimenez-Palomares, Margarita пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Johnson, Jennal пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company; Stock/Shareholder: Eli
Lilly and Company
Johnson, Nicole пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Johnson, Susan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Joly, Erik пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jones-Leone, Angela пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Joung, Kyong-Hye пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jullig, Mia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jung, Dae Young пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Jung, Sangmin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kabagambe, Edmond K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kadowaki, Takashi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Chugai Pharmaceutical Co., Ltd., DainВ­
ippon Sumitomo Pharma Co., Ltd., Merck Sharp &
Dohme Limited, Novartis Pharmaceuticals CorporaВ­
tion, Novo Nordisk, Inc., Ono Pharmaceutical Co., Ltd.,
Sanofi, Takeda Pharmaceutical Company, Ltd.; Speaker’s Bureau: Astellas Pharma Inc., Dainippon Sumi­
tomo Pharma Co., Ltd., Eli Lilly Japan, Kowa PharmaВ­
ceuticals, Merck Sharp & Dohme Limited, Novartis
Pharmaceuticals Corporation, Novo Nordisk, Inc.,
Sanofi, Takeda Pharmaceutical Company, Ltd.
Kaestner, Klaus пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kahn, Richard пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kai, Alan K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kalaj, Anita пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kalil, Roberto пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kampino, Gadi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kang, Ja Hoon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kang, Li пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kang, Seul Gi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kanoni, Stavroula пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kapitza, Christoph пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Astellas, Boehringer Ingelheim GmbH
& Co. KG, Dance Pharmaceuticals, Eli Lilly and ComВ­
pany, Novo Nordisk A/S, Sanofi
Kasichayanula, Sreeneeranj пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Bristol-Myers Squibb Company; Stock/Shareholder: Bristol-Myers Squibb Company
Katić, Maša ����������������������������������������� Disclosed no conflict of interest.
Kato, Seiya пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kaufman, Francine R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Medtronic, Inc.
Kaye, Joey пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Eli Lilly and Company, Novo Nordisk, Inc.,
Sanofi; Research Support: Eli Lilly and Company, Novo
Nordisk, Inc., Sanofi
Kazda, Christof M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company; Stock/Shareholder: Eli
Lilly and Company
Ke, Weijian пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kelly, Ronan P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company; Stock/Shareholder: Eli
Lilly and Company
Kenji, Sugawara пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kennedy, Amy пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kennedy, Robert пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kerr, David пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Khan, Abdul R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kibbey, Richard G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kikuchi, Naoya пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Kilimnik, Jerry пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kilroy, Gail пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Dennis D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Zafgen, Inc.; Stock/Shareholder: Zafgen, Inc.
Kim, Gabriel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
Kim, Grace пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Hae-Suk пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Hyun Jin Kim пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Jason K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Jeong-a пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Jongoh пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Koon Soon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Sarah пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Se Min пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Terri пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Elcelyx Therapeutics, Inc.
Kim, Yong Kyun пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Young Hoon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kim, Young Kyung пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kirby, Brenda пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kirk-Ballard, Heather пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
LB70
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Kishimoto, Junji пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kitazato, Hiroji ������������������������������������� Speaker’s Bureau: Eli Lilly Japan, Merck Sharp & Dohme
Limited, Mitsubishi Tanabe Pharmaceutical CorporaВ­
tion, Novartis Pharmaceuticals Corporation, Sanofi,
Shionogi, Inc.
Kleber, Marcus пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Klonoff, David C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Medtronic, Inc.
Knobf, M. Tish пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Knop, Filip K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ko, Hwi Jin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kobayashi, Yumiko пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kocalis, Heidi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Koh, Angela пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Koh, Eun Kyung пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Koh, Ho-Jin N. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Koh, Pei Ling пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kolatsi-Joannou, Maria пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kolattukudy, Pappachan E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Koliwad, Suneil K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Daiichi Sankyo, Inc.; Research Support:
Merck
Kolka, Cathryn M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kollman, Craig пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Komatsu, Hidetoshi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Kono, Tatsuyoshi M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Koren, Shlomit пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Krager, Stacey пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Krasner, Alan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Biodel, Inc.; Stock/Shareholder: Biodel, Inc.
Krishnarajah, Janakan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Linear Clinical Research
Kruckelmann, Friederike пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kucera, Petr пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kudva, Yogish C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kuhadiya, Nitesh пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kulkarni, Bhushan V. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Ethicon EndoSurgery, Inc.
Kumar, Ashok пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kumar, Ashok R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kumar, Jitender пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kumusoglu, Doga пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kunos, George пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kuo, Shihchen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kurahashi, Kiyoe пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kwee, Lydia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Kwon, Se Chang пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ladenvall, Claes пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Laffel, Lori M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lagakos, William S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lagou, Vasiliki пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lam, Karen Siu Ling пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lam, Tony K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Langer, Jakob пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Novo Nordisk, Inc.; Stock/Shareholder: Novo
Nordisk, Inc.
Langkilde, Anna Maria пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: AstraZeneca Pharmaceuticals
Langslet, Gisle пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Janssen Pharmaceuticals, Inc.
Laron, Zvi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Laron-Kenet, Tamar пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lauritzen, Hans P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Le, Bach пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lebovitz, Harold E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Amylin Pharmaceuticals, Biocon Ltd., IntВ­
arcia, Janssen Pharmaceuticals, Inc., Metacure, Poxel
Pharma; Consultant: AstraZeneca Pharmaceuticals
Bristol-Myers Squibb Company; Stock/Shareholder:
Abbott Laboratories, Merck
Lee, Douglas S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Pfizer, Inc.; Stock/Shareholder: Pfizer, Inc.
Lee, Kyu Hang пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lee, Min Hee пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lee, Min-Young пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lee, Richard G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Isis Pharmaceuticals, Inc.; Stock/Shareholder:
Isis Pharmaceuticals, Inc.
Lee, Soo Jin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lee, Tyson пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: FibroGen, Inc.
Lee, Yongjin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lee, Young-Kyun пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Leelarathna, Lalantha пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lehman, Donna M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Leiter, Lawrence A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: AstraZeneca Pharmaceuticals, Boehringer
Ingelheim GmbH, Bristol-Myers Squibb Company, Eli
Lilly and Company, GlaxoSmithKline, Merck, Novo
Nordisk, Inc., Hoffman-La Roche, Inc., Sanofi, Takeda
Pharmaceutical Company, Ltd.; Research Support:
AstraZeneca Pharmaceuticals, Boehringer Ingelheim
GmbH, Bristol-Myers Squibb Company, Eli Lilly and
Company, GlaxoSmithKline, Merck, Novo Nordisk,
Inc., Hoffman-La Roche, Inc., Sanofi, Takeda PharmaВ­
ceutical Company, Ltd.; Speaker’s Bureau: AstraZen­
RELATIONSHIP/COMPANY
eca Pharmaceuticals, Boehringer Ingelheim GmbH,
Bristol-Myers Squibb Company, Eli Lilly and Company,
GlaxoSmithKline, Merck, Novo Nordisk, Inc., HoffВ­
man-La Roche, Inc., Sanofi, Takeda Pharmaceutical
Company, Ltd.
LeLay, John пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lemon, Stephenie C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Leong, Robert пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: FibroGen, Inc.
Lepouras, Antonios пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lertwattanarak, Raweewan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Levandoski, Lucy пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ley, Sylvia H. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Fangyong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Guohua пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Hai пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Li пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Ling пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Man пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Ning пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Pingping пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Siming пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Weijie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Yanbing пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Li, Yinming пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liang, Hanyu пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liao, Lizhen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liljenquist, David R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lin, Iris пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lin, Jiandie D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lin, Jiang ���������������������������������������������� Employee: Glaxo­Smith­Kline; Stock/Shareholder: Glaxo–
SmithKline
Lin, Yuhong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lipp, Sonia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lipps, Janie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Little, Stuart A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Littlejohn, Elizabeth пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liu, Bing пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liu, Ching-Ti пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liu, De Min пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liu, Jie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liu, Jingmin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liu, Juan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liu, Liehua пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Liu, Rong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company; Stock/Shareholder: Eli
Lilly and Company
Liu, Yaping J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline
Locatelli, Maelle пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Long, David A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
LГіpez AlarcГіn, Mardia Guadalupe пїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lorenzo, Carlos пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lovell-Badge, Robin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lu, Min пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lu, Young пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lubina Solomon, Alexandra пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lum, Helen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lutale, Janet пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lynch, Jane L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lynn, Marissa H. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lysek, Robert пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Lyssenko, Valeriya пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ma, Yunsheng пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
MacDougald, Ormond пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Macias-Gonzalez, Manuel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Madhusudan, R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Madiraju, Murthy пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Maeda, Risa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Maemura, Koji пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Nippon Boehringer Ingelheim Co., Ltd;
Research Support: Astellas Pharma Inc., Daiichi-SanВ­
kyo, Inc., Merck Sharp & Dohme Limited; Speaker’s
Bureau: Astellas Pharma Inc., Bayer Pharmaceuticals,
Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo, Inc.,
Dainippon Sumitomo Pharma Co., Ltd., Kowa PharmaВ­
ceuticals, Kyowa Hakko Kirin Co., Ltd., Merck Sharp &
Dohme Limited, Mitsubishi Tanabe Pharmaceutical
Corporation, Mochida Pharmaceutical Co., Ltd., NipВ­
pon Boehringer Ingelheim Co., Ltd., Novartis PharmaВ­
ceuticals Corporation, Pfizer, Inc., Sanwa Kagaku KenВ­
kyusho Co., Ltd., Shionogi, Inc., Takeda
Pharmaceutical Company, Ltd.
Mägi, Reedik ���������������������������������������� Disclosed no conflict of interest.
Mahajan, Anubha пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Maiya, Arun G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Makdissi, Antoine пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
LB71
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Makino, Hirofumi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Maldonado HernГЎndez, Jorge пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Malone, Kaitlin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Maneva-Radicheva, Lilia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mangiafico, Salvatore пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mani, Arya пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mani, Sheida пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Manojkumar, S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Manson, JoAnn E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mansuy-Aubert, Virginie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mantha, Kamala пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Maranhao, Raul C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Maratos-Flier, Eleftheria пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Novo Nordisk, Inc.
Marchetti, Piero пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Marcheva, Biliana пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Margulies, Kenneth B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mari, Andrea пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Eli Lilly and Company; Research Support:
Boehringer Ingelheim GmbH & Co. KG
Marjason, Joanne пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Marks, Jennifer пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Marks-Shulman, Pamela пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Marquis, Alison пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Sanofi
Marselli, Lorella пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Marshall, Helen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Marshall, Sally M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Martin, Ashley пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Martinez Basila, Azucena пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
MartГ­nez Razo, Gabriel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
MartГ­nez-Basila, Azucena пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Martinez-Gonzalez, Miguel Angel пїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Marukian, Svetlana пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Marullo, Letizia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mathur, Ruchi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Matragoon, Suraporn пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Matsen, Miles E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Matsuda-Nagasumi, Kae пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Matsuzaki, Goro пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Matute GonzГЎlez, MarГ­a Guadalupe пїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mauras, Nelly пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Medtronic, Inc., Pfizer, Inc.
Mauriello, Clifford пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
McAllister, Andres пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
McCall, Anthony L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
McCarthy, Mark I. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
McClain, Donald A. ������������������������������ Speaker’s Bureau: Merck
McDonald, Matthew W. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
McGee, Sean пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
McGettrick, Helen M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
McKee, Elizabeth пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
McNulty, Judi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline
McTigue, Kathleen M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Meek, Thomas H. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mehlburger, Ludwig пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
Mehler, Robert E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: SomaLogic.com
Meier, Juris J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Meigs, James B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Meininger, Gary пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Meister, Daniel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Melito, Julie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: ALPCO Diagnostics
Melling, Jamie W. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Melton, Stephanie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mendrick, Edward пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Menegaz, Danusa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Meng, Zhuoxian пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Meredith, Melissa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Medtronic, Inc.
Merriam, Philip пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Merrins, Matthew пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Miao, Dongmei пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Michaud, AndrГ©anne пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Middleditch, Martin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mihailov, Evelin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Miliˇci’c, Davor ��������������������������������������� Disclosed no conflict of interest.
Miller, Michael E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Miller, Rehae пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Millington, Dawn пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Mills, Joseph L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ming-Jing, Bao пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Minokoshi, Yasuhiko пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mirmira, Raghavendra G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mitchell, Creighton пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mitten, Emilie K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Miyake, Masato пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Miyawaki, Kazumasa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Mo, Xiuu-Lei пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
RELATIONSHIP/COMPANY
Mobley, Sandra пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mohamed, Islam N. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mokhlesi, Babak пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Molano, R. Damaris пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Board Member: Converge Biotech, Inc. (Spouse/Partner),
NEVA Scientific, LLC. (Spouse/Partner); Research Support: ATRM (Spouse/Partner), Converge Biotech, Inc.
(Spouse/Partner), Pfizer, Inc. (Spouse/Partner), PosiВ­
tive ID (Spouse/Partner); Stock/Shareholder: ConВ­
verge Biotech, Inc., Converge Biotech, Inc. (Spouse/
Partner), NEVA Scientific, LLC. (Spouse/Partner)
Molina, Judith T. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Monks, Bob пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Montanya, Eduard пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: AstraZeneca Pharmaceuticals, BristolMyers Squibb Company, Intartia, Novo Nordisk, Inc.;
Employee: Almirall, S.A. (Spouse/Partner)
Monteleone, Jon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Moolemath, Yoganand пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Morahan, Grant пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Moran, Patricia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Moreno-Santos, Inmaculada пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Morgan, Christopher L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mori, Masaaki пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Morin, Johane пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Morris, Andrew P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Morris, David L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Morton, Anna пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Morton, Gregory J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Moskowitz, Judith T. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Moss, Dan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Muehlen-Bartmer, Isabel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Sanofi
Mugabo, Yves пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mukherjee, Jayanti пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Bristol-Myers Squibb Company
Mulvagh, Sharon L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: LipoScience, Inc.
Mumby, Patricia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
MuГ±oz-Garach, Araceli пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Murakami, Kazutoshi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Murphy, Elizabeth пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Murphy, Rinki пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Muscelli, Elza пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Musi, Nicolas пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Muzzin, Patrick пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Mysona, Barbara A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nacher, Montserrat пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Naik, Sarita пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nakamura, Katherine пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Dexcom, Inc.
Nakanishi, Takeo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nakatsuka, Atsuko пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nalls, Michael A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nam, Hong Gil пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Narendran, Parth пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nash, Gerard пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Natarajan, Sundar пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nauck, Michael A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Amylin Pharmaceuticals, Inc., Berlin CheВ­
mie AG, Boehringer Ingelheim Pharmaceuticals, Inc.,
Eli Lilly and Company, GlaxoВ­SmithВ­Kline, Hoffman La
Roche, Inc., Intarcia Therapeutics, Inc., Merck Sharp
& Dohme Limited, Novo Nordisk, Inc., Sanofi, VersarВ­
tis, Inc.; Consultant: Amylin Pharmaceuticals, Inc.,
AstraZeneca Pharmaceuticals LP, Berlin Chemie AG,
Boehringer Ingelheim Pharmaceuticals, Inc., Diartis
Pharmaceuticals, Eli Lilly and Company, GlaxoВ­SmithВ­
Kline, Hoffman La Roche, Inc., Intarcia Therapeutics,
Inc., Janssen Global Services, LLC., Merck Sharp &
Dohme Limited, Novartis Pharmaceuticals CorporaВ­
tion, Novo Nordisk A/S, Sanofi, Versartis, Inc.; Other
Relationship: Boehringer Ingelheim Pharmaceuticals,
Inc., Eli Lilly and Company, MDS, Inc., Medscape,
LLC.; Research Support: AstraZeneca Pharmaceuticals
LP, Boehringer Ingelheim Pharmaceuticals, Inc., GlaxoВ­
SmithВ­Kline, MataCure, Inc., Merck Sharp & Dohme
Limited, Novartis Pharmaceuticals Corporation, Novo
Nordisk, Inc., Roche Pharmaceuticals, ToleRx; Speaker’s Bureau: AstraZeneca Pharmaceuticals LP, Berlin
Chemie AG, Boehringer Ingelheim Pharmaceuticals,
Inc., Eli Lilly and Company, MDS, Inc., Novartis PharВ­
maceuticals Corporation, Novo Nordisk A/S, Roche
Pharmaceuticals
Neff, Thomas B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: FibroGen, Inc.
Negi, Anuradha пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nelson, Chris пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nelson, Michael D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ng, Maggie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nguyen, Dung пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
LB72
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Niemeyer, GГјnter пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Niswender, Kevin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Niu, Jianli пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Noble, Earl G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nobrega, Marcelo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Noda, Mitsuhiko ���������������������������������� Research Support: Daiichi-Sankyo, Inc.; Speaker’s Bureau:
Daiichi-Sankyo, Inc., Dainippon Sumitomo Pharma
Co., Ltd., Merck Sharp & Dohme Limited, Mitsubishi
Tanabe Pharmaceutical Corporation, Mochida PharВ­
maceutical Co., Ltd., Novartis Pharmaceuticals CorpoВ­
ration, Novo Nordisk, Inc., Ono Pharmaceutical Co.,
Ltd., Sanofi, Takeda Pharmaceutical Company, Ltd.
Nomura, Akitoshi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nomura, Daniel K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Norby, Barbra пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ntambi, James пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Nunez, Derek J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
O’Connor-Semmes, Robin L. ���������������� Employee: Glaxo­Smith­Kline; Stock/Shareholder: Glaxo­
SmithВ­Kline
O’Farrell, Libbey ����������������������������������� Employee: Eli Lilly and Company; Stock/Shareholder: Eli
Lilly and Company
Ockene, Ira S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Odawara, Masato пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Bayer Pharmaceuticals, Dainippon
Sumitomo Pharma Co., Ltd., Eli Lilly Japan, Kissei
Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd.,
Mitsubishi Tanabe Pharma Corporation, Mochida
Pharmaceutical Co., Ltd., Nippon Boehringer
Ingelheim Co., Ltd., Novo Nordisk, Inc., Ono PharmaВ­
ceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho
Co., Ltd., Takeda Pharmaceutical Company, Ltd.;
Speaker’s Bureau: Bayer Pharmaceuticals, Dainippon
Sumitomo Pharma Co., Ltd., Eli Lilly Japan, Kissei
Pharmaceutical Co., Ltd., Kowa Pharmaceuticals,
Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe
Pharma Corporation, Mochida Pharmaceutical Co.,
Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo
Nordisk, Inc., Ono Pharmaceutical Co., Ltd., Sanofi,
Sanwa Kagaku Kenkyusho Co., Ltd., Takeda PharmaВ­
ceutical Company, Ltd.
Ogawa, Daisuke пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ogura, Atsushi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Oh, Dayoung пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ohta, Yasuharu пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Oiso, Yutaka пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Okutsu, Mitsuharu пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Olausson, Eva A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Olefsky, Jerrold M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Olendzki, Barbara пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Oleski, Jessica пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Oliveira, Alexandre G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Olsen, Sandra E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Olver, Dylan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Omura, Chiaki пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Onthank, Christine пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: ALPCO Diagnostics
Ordronneau, Paul пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Orentreich, David пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Orentreich, Norman пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ostricˇ ki, Branko ������������������������������������ Disclosed no conflict of interest.
Otvos, James пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Oyadomari, Miho пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Oyadomari, Seiichi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Pagoto, Sherry пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
PairГі, Mar пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Palau-Collazo, Miladys пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Pan, Jiaqi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Parikh, Grishma пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Parikh, Shamik J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: AstraZeneca Pharmaceuticals LP
Park, Chang пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Park, Chanmi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Park, Hanjong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Park, Soo-Young пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Park, Sung Hee пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Parker, Camille пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Parra, Esteban пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Parrott, Abbey пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Pate, Virginia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: GlaxoВ­SmithВ­Kline, Sanofi
Patel, Sanjay пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
Patsouris, David пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Paulmurugan, Ramasamy пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Pawar, Taranveer K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Peffers, Mark пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
RELATIONSHIP/COMPANY
Penckofer, Sue пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Perkins, Christopher пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Pharmaceutical Product Development; Other
Relationship: Fees payable directly to Pharmaceutical
Product Development for data monitoring boards, staВ­
tistical analyses, end point committees; Stock/Shareholder: GlaxoВ­SmithВ­Kline
Perkovic, Vlado пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Abbot, Astellas, Boehringer Ingelheim
Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.,
Pfizer, Inc.
Perrone, Carmen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Perry, Caroline пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Peterson, Richard G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Preclinomics
Peyot, Marie-line пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Phagoo, Steve B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Phinney, Stephen D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Pichotta, Philip пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Biodel, Inc.; Stock/Shareholder: Biodel, Inc.
Pileggi, Antonello пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Board Member: Converge Biotech, Inc., NEVA Scientific,
LLC.; Research Support: ATRM, Pfizer, Inc., Positive ID,
LLC.; Stock/Shareholder: Converge Biotech, Inc., ConВ­
verge Biotech, Inc. (Spouse/Partner), NEVA Scientific,
LLC.
Pirags, Valdis пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Pollock, Brad пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Pongratz, Rebecca L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Poretsky, Leonid пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Port, John пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Powell, Blair пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Prabhakar, Bellur пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Pratley, Richard пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: AstraZeneca Pharmaceuticals LP, Eisai, Inc.,
GlaxoВ­SmithВ­Kline, Lexicon Pharmaceuticals, Inc.,
MannKind Corporation, Merck, Novartis PharmaceuВ­
ticals Corporation, Novo Nordisk, Inc., Roche PharВ­
maceuticals, Sanofi, Takeda Pharmaceuticals U.S.A.,
Inc.; Research Support: Eli Lilly and Company, GlaxoВ­
SmithВ­Kline, MannKind Corporation, Merck, Novartis
Pharmaceuticals Corporation, Novo Nordisk, Inc.,
Pfizer, Inc., Roche Pharmaceuticals, Sanofi, Takeda
Pharmaceuticals U.S.A., Inc.; Speaker’s Bureau:
Merck
Praw, Stephanie S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Prentki, Marc пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Prentki, RaphaГ«l пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Price, Karen L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Prigeon, Ronald пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Prochazkova, Zdenka пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Proietto, Joe пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Prokopenko, Inga пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Prud’Homme, Denis ����������������������������� Disclosed no conflict of interest.
Puppala, Sobha пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Qu, Liming пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Quehenberger, Oswald пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Quinn, Laurie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Qureshi, Sheeraz A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ra, Ho пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rabasa-Lhoret, Remi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rabinovitz, Rona пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Radichev, Ilian пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rainger, George E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ramires, Jose пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ramkumar, Kunka Mohanram пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ramsey, Kathryn M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ran, Nina пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ranganath, L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rasku, Julie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: ALPCO Diagnostics
Rasouli, Neda пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rayfield, Eliot J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Raymond, Ralph H. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rayner, Nigel W. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Reddivari, Lavanya пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Reinhardt, Rickey пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Reiss, Allan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rendell, Marc пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Other Relationship: Grants for multiple multicenter trials
payable to Creighton University, Study Grants for AlbiВ­
glutide payable to Creighton University
Reusch, Jane пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Biomedical Research Foundation of Colorado,
payable to institution directly; Other Relationship:
Meeting travel, Biomedical Research Foundation of
Colorado, payable to institution directly
Rewers, Marian J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rexrode, Kathryn M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rezende, Paulo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
LB73
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Rhodes, Christopher J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rice, David пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: ALPCO Diagnostics
Richards, Louise пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ricordi, Camillo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Board Member: Converge Biotech, Inc., NEVA Scientific,
LLC., Ophysio; Research Support: ATRM; Stock/Shareholder: Converge Biotech, Inc., NEVA Scientific, LLC.,
Ophysio
Riddle, Matthew C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Amylin Pharmaceuticals, Inc., Elcelyx TheraВ­
peutics, Inc., Eli Lilly and Company, Sanofi, Valeritas,
LLC.; Research Support: Amylin Pharmaceuticals, Inc.,
Elcelyx Therapeutics, Inc., Eli Lilly and Company,
Sanofi, Valeritas, LLC.
Rieck, Sebastian пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ried, Janina пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rimm, Eric B. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ripatti, Samuli пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Roberson, Tamara M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Roberts, Brian K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: FibroGen, Inc.
Robertson, R. Paul �������������������������������� Speaker’s Bureau: Merck
Rodgers Fischl, Andrea пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rodriguez, Maria Antonia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rodriguez-Diaz, Rayner пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rodriguez-Sosa, Miriam пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Roggerio, Alessandra пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rohn, Reuben пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rohwedder, Katja пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: AstraZeneca Pharmaceuticals LP
Rosen, Rosen D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rosenstock, Julio пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Boehringer Ingelheim Pharmaceuticals,
Inc., Daiichi-Sankyo, Inc., Eli Lilly and Company,
GlaxoВ­SmithВ­Kline, Intarcia Therapeutics, Inc., Johnson
& Johnson Services, Inc., Lexicon Pharmaceuticals,
Inc., MannKind Corporation, Merck, Novartis PharmaВ­
ceuticals Corporation, Novo Nordisk, Inc., Roche PharВ­
maceuticals, Sanofi, Takeda Pharmaceuticals U.S.A.,
Inc.; Consultant: Boehringer Ingelheim PharmaceutiВ­
cals, Inc., Daiichi-Sankyo, Inc., Eli Lilly and Company,
GlaxoВ­SmithВ­Kline, Intarcia Therapeutics, Inc., Johnson
& Johnson Services, Inc., Lexicon Pharmaceuticals,
Inc., MannKind Corporation, Merck, Novartis PharmaВ­
ceuticals Corporation, Novo Nordisk, Inc., Roche PharВ­
maceuticals, Sanofi, Takeda Pharmaceuticals U.S.A.,
Inc.; Research Support: Amylin Pharmaceuticals, Inc.,
Boehringer Ingelheim Pharmaceuticals, Inc., BristolMyers Squibb Company, AstraZeneca PharmaceutiВ­
cals, Daiichi-Sankyo, Inc., Eli Lilly and Company,
GlaxoВ­SmithВ­Kline, Intarcia Therapeutics, Inc., Janssen
Pharmaceuticals, Inc., Johnson & Johnson Services,
Inc., Lexicon Pharmaceuticals, Inc., MannKind CorpoВ­
ration, Merck, Novartis Pharmaceuticals Corporation,
Novo Nordisk, Inc., Pfizer, Inc., Roche PharmaceutiВ­
cals, Sanofi, Takeda Pharmaceuticals U.S.A., Inc.
Rotenstein, Lisa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Roy, Anirban пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Medtronic MiniMed, Inc.
Rubin, Daniel J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ruedy, Katrina пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ruiz, Michael A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ruzzin, Jerome пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rybin, Denis пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Rypackova, Blanka пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Saad, Mario J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Saad, Sara O. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Saenger, Amy K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sakai, Soichi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sakuma, Kensuke пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Sakuma, Toshie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Salas-FernГЎndez, Alejandra пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Salazar, Tatiana пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Salsali, Afshin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
Sammeth, Michael пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Samukawa, Yoshishige пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
San JosГ© TerrГіn, Patricia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sanchez-Zamora, Yuriko Itzel пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sandhu, Sartaj пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sandoval, Darleen A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Ethicon EndoSurgery, Inc.
Sarin, Antti-Pekka пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Saslow, Laura пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Satin, Leslie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sato, Ryosuke пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Savinov, Alexei Y. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Diamedica, Inc.
Savoye, Mary пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Schenk, Simon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Schernthaner, Guntram пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Scheys, Joshua пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
RELATIONSHIP/COMPANY
Schmitt, Patricia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Schneider, Kristin L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Scholl, Theresa O. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Schwartz, Gary пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Schwartz, Michael W. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Schwarz, Sarah пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Seeley, Randy J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Ethicon EndoSurgery, Inc.; Research Support:
Ethicon EndoSurgery, Inc.; Speaker’s Bureau: Ethicon
EndoSurgery, Inc.
Seggelke, Stacey A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Segre, Alexandre пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Seino, Susumu пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sekar, Thillai V. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sereika, Susan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sesso, Howard D. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Seymour, Heidi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Shaffer-Hudkins, Emily пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Shariat-Madar, Zia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sharma, Sumit пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Shastry, Barkur A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Shaw, James A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Medtronic, Inc.; Other Relationship: Novo
Nordisk, Inc.; Research Support: Diabetes UK, Dompe,
Diabetes Research and Wellness Foundation, JuveВ­
nile Diabetes Research Foundation
Shaw, Melissa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Shaw, Wayne пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Shekiro, Kelly M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Shelton, Richard C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sherr, Jennifer L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sherwin, Robert S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Shiba, Teruo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Merck Sharp & Dohme Limited, Sanofi,
Shionogi, Inc., Takeda Pharmaceutical Company, Ltd.;
Speaker’s Bureau: Eli Lilly Japan, Kowa Pharmaceuti­
cals, Merck Sharp & Dohme Limited, Mochida PharВ­
maceutical Co., Ltd., Nippon Boehringer Ingelheim
Co., Ltd., Novartis Pharmaceuticals Corporation,
Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Takeda
Pharmaceutical Company, Ltd.
Shibasaki, Tadao пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Shin, Chan Soo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Shoemaker, Kevin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Shong, Minho пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Signal, Matthew пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Simcox, Judith пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Simms, Patrick пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Biodel, Inc.; Stock/Shareholder: Biodel, Inc.
Simon, Jacan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
SimrГ©n, Magnus пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sims, Emily K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sinclair, Alan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Eli Lilly and Company, Merck Sharp &
Dome Corp., Novartis Pharmaceuticals Corporation,
Takeda Pharmaceutical Company, Ltd.; Speaker’s
Bureau: Eli Lilly and Company, Merck Sharp & Dome
Limited, Novartis Pharmaceuticals Corporation,
Takeda Pharmaceutical Company, Ltd.
Singer, Britta пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: SomaLogic, Inc.
Singh, Jaideep пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Singh, Rajvir пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Singh, S.K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Singleton, Walter пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Isis Pharmaceuticals, Inc.; Stock/Shareholder:
Isis Pharmaceuticals, Inc.
Siraj, Elias S. ���������������������������������������� Advisory Panel: Sanofi; Consultant: Corcept; Speaker’s
Bureau: Boehringer Ingelheim Pharmaceuticals, Inc.,
Merck
Skare, Sharon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Elcelyx Therapeutics, Inc.
Skrepnek, Grant H. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sloan, Jeanne M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Slover, Robert пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Medtronic, Inc.
Smillie, Sarah J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Smith, Greg пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Smith, Kenneth J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Smith, Steven R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Snead, Wanda пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Somesh, B.P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Son, JeeWoong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sonenberg, Nahum пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Song, Yiqing пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Spann, Nathanael J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Speight, Jane пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Accu-Chek, Roche Diagnostics AustraВ­
lia, Sanofi; Consultant: Roche Diagnostics AustraВ­
lia, Sanofi; Research Support: Sanofi
Sprandel, Marilia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Steck, Andrea K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Stefanovski, Darko пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
LB74
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Stephens, Heather пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Stewart, Alex пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: SomaLogic, Inc.
Stewart, Murray пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Stocken, Deborah пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Stone, Libby пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Storsrud, Stine пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Strawbridge, Rona J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Striker, Gary E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Sanofi; Consultant: Sanofi; Research Support: Sanofi
Strunz, Celia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Stull, Natalie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sturmer, Til пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Genentech, Inc., GlaxoВ­SmithВ­Kline;
Research Support: GlaxoВ­SmithВ­Kline, Merck, Sanofi
Sum, Chee Fang пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sun, Qi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sun, Weiping пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sun, Zilin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sunil, V. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Surakka, Ida пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Survant, Libby пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sutter, Jennifer A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Swamy, Shobha пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Sweeney, Grace пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Szczepaniak, Edward W. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Szczepaniak, Lidia S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tabrizian, Tahmineh пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Taegtmeyer, Heinrich пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tai, Andrew C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Takahara, Kazuna пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Takahashi, Harumi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Takahashi, Toshimasa пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Takeuchi, Koji пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Talukdar, Saswata пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tam, Sidney пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tamai, Ikumi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tamboli, Robyn A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tamborlane, William V. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Animas Corporation, Bristol-Myers Squibb
Company, Medtronic MiniMed, Inc.; Speaker’s
Bureau: Novo Nordisk, Inc.; Stock/Shareholder: InsuВ­
line Medical
Tamler, Ronald пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tan, Horng Kai пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tanenberg, Robert J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Eli Lilly and Company, MannKind CorВ­
poration, Sanofi; Speaker’s Bureau: Boehringer
Ingelheim Pharmaceuticals, Inc., Sanofi
Tanizawa, Yukio пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tao, Ya-Xiong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tasali, Esra пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tchernof, AndrГ© пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
TГ©llez, Noelia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Terami, Naoto пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Terami, Takahiro пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Terauchi, Yasuo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Boehringer Ingelheim Japan, Inc., Chugai
Pharmaceutical Co., Ltd., Eli Lilly Japan, Mochida
Pharmaceutical Co., Ltd., Novo Nordisk, Inc., Pfizer,
Inc., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd;
Research Support: Astellas Pharma Inc., Bayer PharВ­
maceuticals, Boehringer Ingelheim Japan, Inc., DaiВ­
ichi-Sankyo, Inc., Dainippon Sumitomo Pharma Co.,
Ltd., Eli Lilly Japan, Kissei Pharmaceutical Co., Ltd.,
Kowa Pharmaceuticals, Merck Sharp & Dohme LimВ­
ited, Mitsubishi Tanabe Pharmaceutical Corporation,
Novartis Pharmaceuticals Corporation, Novo Nordisk,
Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa
Kagaku Kenkyusho Co., Ltd., Shionogi, Inc., Takeda
Pharmaceutical Company, Ltd.; Speaker’s Bureau:
Astellas Pharma Inc., AstraZeneca Pharmaceuticals,
Bayer Pharmaceuticals, Boehringer Ingelheim Japan,
Inc., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo,
Inc., Dainippon Sumitomo Pharma Co., Ltd., Eli Lilly
Japan, Kissei Pharmaceutical Co., Ltd., Kowa PharmaВ­
ceuticals, Merck Sharp & Dohme Limited, Mitsubishi
Tanabe Pharmaceutical Corporation, Novartis PharmaВ­
ceuticals Corporation, Novo Nordisk, Inc., Ono PharВ­
maceutical Co., Ltd., Pfizer, Inc., Sanofi, Sanwa
Kagaku Kenkyusho Co., Ltd., Shionogi, Inc., Takeda
Pharmaceutical Company, Ltd.
Tersey, Sarah A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Thankamony, Ajay пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Thatava, Tayaramma пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Theuerkauf, Anett пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Thomas, Abraham пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
RELATIONSHIP/COMPANY
Thomas, Joshua пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Thorleifsson, Gudmar пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: deCODE Genetics
Tichy, Eileen M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tinahones, Francisco J. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tirri, Lauren пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tischkau, Shelley пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tobacman, Joanne K. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tobe, Kazuyuki пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Astellas Pharma Inc., Mitsubishi
Sanofi, Takeda Pharmaceutical Company, Ltd., Tanabe
Pharmaceutical Corporation; Speaker’s Bureau: Astel­
las Pharma Inc., Boehringer Ingelheim Japan, Inc.,
Daiichi Sankyo, Inc., Dainippon Sumitomo Pharma
Co., Ltd., Eli Lilly Japan, Kowa Pharmaceuticals,
Merck Sharp & Dohme Limited, Mitsubishi Tanabe
Pharmaceutical Corporation, Mochida Pharmaceutical
Co., Ltd., Novo Nordisk, Inc., Ono Pharmaceutical Co.,
Ltd., Sanofi
Todd, Jennifer пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tong, Xin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tonne, Jason пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Toplek, Goran пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Torres, Jason M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Toschi, Elena пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Touma, Carol пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Trautmann, Michael пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tsalikian, Eva пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: Novo Nordisk, Inc., Sanofi
Tso, Patrick пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tsujihata, Yoshiyuki пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Turksoy, Kamuran пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Tzur, Dorit пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Uenishi, Eitai пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Umland, Oliver пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Unterman, Terry G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
UrbanovГЎ, Jana пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Uribarri, Jaime пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Usiskin, Keith пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Valdearcos, Martin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Valledares-Salagado, Adan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Van Bavel, Bert пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Van Cauter, Eve пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Van Iperen, Erik P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Van Zuydam, Natalie пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Vanamala, Jairam пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Vander Heiden, Matthew G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Vassy, Jason L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Vath, James E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Zafgen, Inc.; Stock/Shareholder: Zafgen, Inc.
Venkataranganna, M.V. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Vercruysse, Frank пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Vergani, Andrea пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Vernon, Marlo пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Vijapurkar, Ujjwala пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Vilches-Flores, Alonso пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
VilsbГёll, Tina пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Vlachopoulou, Efthymia пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Vlassara, Helen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Voight, Benjamin F. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Von Eynatten, Maximilian пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
Von Holtey, Maria пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Vora, Jiten пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Abbott Laboratories, Inc., Eli Lilly and
Company, Merck Sharp & Dohme Limited, Novartis
Pharmaceuticals Corporation, Novo Nordisk A/S,
Sanofi; Research Support: Merck Sharp & Dohme LimВ­
ited, Novo Nordisk A/S, Sanofi; Speaker’s Bureau: Eli
Lilly and Company, Merck Sharp & Dohme Limited,
Novartis Pharmaceuticals Corporation, Novo Nordisk
A/S, Sanofi
Wada, Jun пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Walder, Ken пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Walker, Lucy пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Walkinshaw, Emma пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wallen, Taylor пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wallis, Diane пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wamhoff, Brian пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wang, Binhuan пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wang, Cecilia L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wang, Chen-Pin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Research Support: National Cancer Institute
Wang, Chun пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wang, Fei пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wang, Jianxin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wang, Lin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wang, Lu пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wang, Xiangfei пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wang, Ying пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
LB75
AUTHOR
RELATIONSHIP/COMPANY
AUTHOR
Wang, Yunjiao пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Waring, Molly пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wasserman, David H. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Waters, Thaddeus P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Watkins, Steven M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Webster, Zoe пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Weinzimer, Stuart A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: Animas Corporation; Consultant: Becton,
Dickinson and Company; Research Support:
Medtronic MiniMed, Inc.; Speaker’s Bureau: Eli Lilly
and Company; Stock/Shareholder: Insuline Medical
Weiss, Elizabeth пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: ALPCO Diagnostics
Wencker, Detlef пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Weyman, Kate пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Whately-Smith, Caroline пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Consultant: Sanofi
White, Amanda T. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
White, Kathryn E. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
White, Michael G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Whited, Matthew C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wilkinson, Helen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Willems, Sara M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Willenborg, Christina пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Williams, Brandon пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Williams, Mark пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Diamedica, Inc.
Williams, Stephen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: SomaLogic, Inc.
Wilson, Craig пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Global Research & Development CenВ­
ter, Inc.
Wilson, Darrell M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wilson, James G. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Winkler, Thomas W. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wisherd, Chris пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: ALPCO Diagnostics
Witkowski, Piotr пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Woerle, Hans-Juergen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Boehringer Ingelheim GmbH & Co. KG
Woo, Vincent пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Advisory Panel: AstraZeneca Pharmaceuticals, Boehringer
Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb
Company, Eli Lilly and Company, Janssen PharmaceuВ­
ticals, Inc., Merck, Novo Nordisk, Inc., Sanofi;
Research Support: AstraZeneca Pharmaceuticals,
Boehringer Ingelheim Pharmaceuticals, Inc., BristolMyers Squibb Company, Eli Lilly and Company, JansВ­
sen Pharmaceuticals, Inc., Merck, Novo Nordisk, Inc.,
Sanofi; Speaker’s Bureau: AstraZeneca Pharmaceuti­
cals, Boehringer Ingelheim Pharmaceuticals, Inc.,
Bristol-Myers Squibb Company, Eli Lilly and Company,
Janssen Pharmaceuticals, Inc., Merck, Novo Nordisk,
Inc., Sanofi
Wood, Ruth пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Woodlief, Tracey пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Woods, Stephen C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Woodward, Mark пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Woolf, Adrian S. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wu, Qiang пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Wylie-Rosett, Judith пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Xie, John пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Janssen Research & Development, LLC.
Xie, Xiangyang пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
RELATIONSHIP/COMPANY
Xiong, Keming пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Xu, Aimin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Xu, Allison W. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Xu, Can-Xin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Xu, Jianfeng пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Xu, Min пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yabuki, Chiori пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Takeda Pharmaceutical Company, Ltd.
Yamaguchi, Jun-ichi пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yamazaki, Tsutomu ������������������������������� Research Support: AstraZeneca Pharmaceuticals; Speaker’s Bureau: AstraZeneca Pharmaceuticals, DaiichiSankyo, Inc., Dainippon Sumitomo Pharma Co., Ltd.,
Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme
Limited, Mitsubishi Tanabe Pharma Corporation,
Novartis Pharmaceuticals Corporation, Pfizer, Inc.,
Shionogi, Inc., Takeda Pharmaceutical Company, Ltd.
Yan, Yuanqing пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yan, Zhen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yanek, Lisa R. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yang, Fred пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Yang, Guang-Ran пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yang, Jiayue пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yap, Mee Li пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yarborough, OrLando пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yarchoan, Mark пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yates, Clara M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ye, June пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline; Stock/Shareholder: GlaxoВ­
SmithВ­Kline
Yip, Shelley пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yoon, Kun-Ho пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yoshimura, Akihiko пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Younce, Craig W. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Young, Andrew A. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: GlaxoВ­SmithВ­Kline
Young-Hyman, Deborah L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yu, Kin-Hung P. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: FibroGen, Inc.
Yu, Liping пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yu, Maria пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Eli Lilly and Company
Yubero-Serrano, Elena M. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Yue, Jessica T. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zgibor, Janice C. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhang, Hui пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhang, Kehao пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhang, Lu пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhang, Sarah X. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhang, Yang пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhang, Yurong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhang, Zhenzhen пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhao, Ruxing пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhao, Shangang пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhao, Xiaojian пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhao, Xiaolong пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhong, Yimin пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Zhou, Qiong L. пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Disclosed no conflict of interest.
Ziemen, Monika пїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅпїЅ Employee: Sanofi
LB76
SAVE THE DATE!
Join us in San Francisco for the
74th Scientific Sessions
June 13–17, 2014
Moscone Center
IMPORTANT DATES TO REMEMBER
Abstract submission site opens in early October 2013
Registration and Housing open in December 2013
Abstract submission site closes in early January 2014
SEE YOU IN SAN FRANCISCO!
Visit scientificsessions.diabetes.org for more information.

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